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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/11 11:55:51」(JST)
wiki ja
BRCA2（breast cancer susceptibility gene II)とは、がん抑制遺伝子の一種であり、その変異により遺伝子不安定性を生じ、最終的に乳癌を引き起こす。
目次
- 1 遺伝子座
- 2 病理
- 3 参考文献
- 4 関連項目
遺伝子座
13番染色体の13q12-13に位置し27個のエクソンからなる。BRCA1同様第11エクソンが非常に大きい。ヒトのBRCA2は3418個のアミノ酸からなる分子量約384kDaのタンパク質[1]。
病理
- C末端側に核移行シグナルが存在し、正常BRCA2は核に存在するが、遺伝子変異をきたしたBRCA2は核に移行できない。BRCA2が正常に機能しない細胞ではDNA損傷が修復されず蓄積してゆく[2]。
- BRCA2変異を伴う家族性乳癌家系では、若年性乳癌のほかに、男性乳癌や卵巣癌の併発も多い。男性乳癌を伴う家族性乳癌のほとんどにBRCA2の変異が見られる。
- BRCA2 変異は東ヨーロッパに祖先を持つユダヤ人（アシュケナージジュー）に多く見られる。29 世代前（約3000 年前）、彼らのBRCA2 遺伝子に欠損を生じたと考えられている。現在、アシュケナージジューの1％にこの遺伝子変異が存在する推測されている。[3]
- BRCA2 は腫瘍抑制遺伝子であり、BRCA2変異があると乳癌のほか卵巣癌、前立腺癌、膵臓癌を発症しやすくなる。
- ユダヤ人の膵癌の1 割にこの変異があるといわれる。BRCA2 変異があると80 歳までに膵癌を発症するリスクが5%から10％と推測されている。
参考文献
- ^ “BRCA2 breast cancer 2, early onset (Homo sapiens)” (英語). National Center for Biotechnology Information, U.S. National Library of Medicine (2011年4月11日). 2011年4月14日閲覧。
- ^ 三木義男 家族性乳癌原因遺伝子 戸井雅和編「乳癌の基礎と臨床」p35-43
- ^ Pancreatic cancer. Lancet (378)9791,607-620, 2011. doi:10.1016/S0140-6736(10)62307-0
関連項目
- がん抑制遺伝子
- 乳癌
| この項目は、医学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:医学／Portal:医学と医療）。 |
wiki en
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| Aliases | BRCA2, BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD, FANCD1, GLM3, PNCA2, XRCC11, breast cancer 2 | ||||||||||||||||
| External IDs | MGI: 109337 HomoloGene: 41 GeneCards: 675 | ||||||||||||||||
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| Location (UCSC) | Chr 13: 32.32 – 32.4 Mb | Chr 5: 150.52 – 150.57 Mb | |||||||||||||||
| PubMed search | [1] | [2] | |||||||||||||||
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crystal structure of a rad51-brca2 brc repeat complex
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| Symbol | BRCA2 | ||||||||
| Pfam | PF00634 | ||||||||
| InterPro | IPR002093 | ||||||||
| SCOP | 1n0w | ||||||||
| SUPERFAMILY | 1n0w | ||||||||
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structure of a brca2-dss1 complex
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| Symbol | BRCA-2_helical | ||||||||
| Pfam | PF09169 | ||||||||
| InterPro | IPR015252 | ||||||||
| SCOP | 1iyj | ||||||||
| SUPERFAMILY | 1iyj | ||||||||
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structure of a brca2-dss1 complex
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| Symbol | BRCA-2_OB1 | ||||||||
| Pfam | PF09103 | ||||||||
| InterPro | IPR015187 | ||||||||
| SCOP | 1iyj | ||||||||
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structure of a brca2-dss1 complex
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| Symbol | BRCA-2_OB3 | ||||||||
| Pfam | PF09104 | ||||||||
| InterPro | IPR015188 | ||||||||
| SCOP | 1iyj | ||||||||
| SUPERFAMILY | 1iyj | ||||||||
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structure of a brca2-dss1 complex
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| Symbol | Tower | ||||||||
| Pfam | PF09121 | ||||||||
| InterPro | IPR015205 | ||||||||
| SCOP | 1mje | ||||||||
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BRCA2 and BRCA2 (/ˌbrækəˈtuː/[1]) are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (breast cancer 2) are maintained by the HGNC. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex. Orthologs, styled Brca2 and Brca2, are common in other mammal species.[2] BRCA2 is a human tumor suppressor gene[3][4] (specifically, a caretaker gene), found in all humans; its protein, also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA.[5]
BRCA2 and BRCA1 are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double strand breaks.[6][7] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer.[8][9] Thus, although the terms "breast cancer susceptibility gene" and "breast cancer susceptibility protein" (used frequently both in and outside the medical literature) sound as if they describe a proto-oncogene or oncogene, BRCA1 and BRCA2 are "normal"; it is their mutation that is abnormal.
The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3).[10] The human reference BRCA 2 gene contains 28 exons, and the cDNA has 10,254 base pairs[11] coding for a protein of 3418 amino acids.[12][13]
The gene was first cloned by scientists at Myriad Genetics, Endo Recherche, Inc., HSC Research & Development Limited Partnership, and the University of Pennsylvania.[14]
Methods to diagnose the likelihood of a patient with mutations in BRCA1 and BRCA2 getting cancer were covered by patents owned or controlled by Myriad Genetics.[15][16] Myriad's business model of exclusively offering the diagnostic test led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012;[17] it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[18]
Contents
- 1 Function
- 2 Clinical significance
- 3 History
- 4 Germ line BRCA2 mutations and founder effect
- 5 Meiosis
- 5.1 BRC repeat sequences
- 6 Neurogenesis
- 7 Epigenetic control of BRCA2
- 8 BRCA2 expression in cancer
- 9 Interactions
- 10 Domain architecture
- 11 Patents, enforcement, litigation, and controversy
- 12 See also
- 13 References
- 14 Further reading
- 15 External links
Function
Recombinational repair of DNA double-strand damage - some key steps. ATM (ATM) is a protein kinase that is recruited and activated by DNA double-strand breaks. DNA double-strand damages also activate the Fanconi anemia core complex (FANCA/B/C/E/F/G/L/M).[19] The FA core complex monoubiquitinates the downstream targets FANCD2 and FANCI.[20] ATM activates (phosphorylates) CHEK2 and FANCD2[21] CHEK2 phosphorylates BRCA1.[22] Ubiquinated FANCD2 complexes with BRCA1 and RAD51.[23] The PALB2 protein acts as a hub,[24] bringing together BRCA1, BRCA2 and RAD51 at the site of a DNA double-strand break, and also binds to RAD51C, a member of the RAD51 paralog complex RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2). The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.[25] RAD51 plays a major role in homologous recombinational repair of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a single strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.
Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. The proteins made by both genes are essential for repairing damaged DNA (see Figure of recombinational repair steps). BRCA2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion a vital step of homologous recombination. The localization of RAD51 to the DNA double-strand break requires the formation of BRCA1-PALB2-BRCA2 complex. PALB2 (Partner and localizer of BRCA2)[26] can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.[27] These breaks can be caused by natural and medical radiation or other environmental exposures, but also occur when chromosomes exchange genetic material during a special type of cell division that creates sperm and eggs (meiosis). Double strand breaks are also generated during repair of DNA cross links. By repairing DNA, these proteins play a role in maintaining the stability of the human genome and prevent dangerous gene rearrangements that can lead to hematologic and other cancers.
Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development.
Clinical significance
Further information: BRCA mutation
Certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormal and does not function properly. Researchers believe that the defective BRCA2 protein is unable to fix DNA damages that occur throughout the genome. As a result, there is an increase in mutations due to error-prone translesion synthesis past un-repaired DNA damages, and some of these mutations can cause cells to divide in an uncontrolled way and form a tumor.
People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia (a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression (reduced blood cell production that leads to anemia). Women having inherited a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1 and BRCA2 associated hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to carcinogens and an infectious process. An innate genomic deficit impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond BRCA1 or BRCA2. A major advantage of this model is that it suggests there are some options in addition to prophylactic surgery.[28]
In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian, Fallopian tube, prostate, and pancreatic cancers, as well as malignant melanoma. In some studies, mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene. Several other types of cancer have also been seen in certain families with BRCA2 mutations.
In general, strongly inherited gene mutations (including mutations in BRCA2) account for only 5-10% of breast cancer cases; the specific risk of getting breast or other cancer for anyone carrying a BRCA2 mutation depends on many factors.[29]
History
| The BRCA2 gene was discovered in 1994 by Professor Michael Stratton along with 39 coauthor scientists[30] (Institute of Cancer Research, UK).[10][31] Scientists from several institutions, including the Wellcome Trust Sanger Institute (Hinxton, Cambs, UK) collaborated with Stratton to isolate the gene.
In honour of this discovery and collaboration, the Wellcome Trust participated in the construction of a cycle and foot path between the Addenbrooke's Hospital site in Cambridge and the nearby village of Great Shelford in 2005. The path by Cambridgeshire County Council and Sustrans is decorated with 10,257 stripes of 4 colours representing the nucleotide sequence of BRCA2 (green representing adenine, blue representing cytosine, yellow representing guanine, and red representing thymine).[32] It makes up part of National Cycle Route 11, and can be seen from trains running between Cambridge and London. |
File:DNA cyclepath to Shelford - geograph.org.uk - 538440.jpg
The start of the cycle path |
Germ line BRCA2 mutations and founder effect
All germ line BRCA2 mutations identified to date have been inherited, suggesting the possibility of a large "founder" effect in which a certain mutation is common to a well-defined population group and can theoretically be traced back to a common ancestor. Given the complexity of mutation screening for BRCA2, these common mutations may simplify the methods required for mutation screening in certain populations. Analysis of mutations that occur with high frequency also permits the study of their clinical expression.[33] A striking example of a founder mutation is found in Iceland, where a single BRCA2 (999del5) mutation accounts for virtually all breast/ovarian cancer families.[34][35] This frame-shift mutation leads to a highly truncated protein product. In a large study examining hundreds of cancer and control individuals, this 999del5 mutation was found in 0.6% of the general population. Of note, while 72% of patients who were found to be carriers had a moderate or strong family history of breast cancer, 28% had little or no family history of the disease. This strongly suggests the presence of modifying genes that affect the phenotypic expression of this mutation, or possibly the interaction of the BRCA2 mutation with environmental factors. Additional examples of founder mutations in BRCA2 are given in the table below.
This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.
| Population or subgroup | BRCA2 mutation(s)[33][36] | Reference(s) |
|---|---|---|
| Ashkenazi Jewish | 6174delT | [37] |
| Dutch | 5579insA | [38] |
| Finns | 8555T>G, 999del5, IVS23-2A>G | [39][40] |
| French Canadians | 8765delAG, 3398delAAAAG | [41][42][43] |
| Hungarians | 9326insA | [44] |
| Icelandics | 999del5 | [34][35] |
| Italians | 8765delAG | [45] |
| Northern Irish | 6503delTT | [46] |
| Pakistanis | 3337C>T | [47] |
| Scottish | 6503delTT | [46] |
| Slovenians | IVS16-2A>G | [48] |
| Spanish | 3034delAAAC(codon936), 9254del5 | [49] |
| Swedish | 4486delG | [50] |
Meiosis
In the plant Arabidopsis thaliana, loss of the BRCA2 homolog AtBRCA2 causes severe defects in both male meiosis and in the development of the female gametocyte.[51] AtBRCA2 protein is required for proper localization of the synaptonemal complex protein AtZYP1 and the recombinases AtRAD51 and AtDMC1. Furthermore, AtBRCA2 is required for proper meiotic synapsis. Thus AtBRCA2 is likely important for meiotic recombination. It appears that AtBRCA2 acts during meiosis to control the single-strand invasion steps mediated by AtRAD51 and AtDMC1 occurring during meiotic homologous recombinational repair of DNA damages.[51]
Homologs of BRCA2 are also essential for meiosis in the fungus Ustilago maydis,[52] the worm Caenorhabditis elegans,[53][54] and the fruitfly Drosophila melanogaster.[55]
Mice that produce truncated versions of BRCA2 are viable but sterile.[56] BRCA2 mutant rats have a phenotype of growth inhibition and sterility in both sexes.[57] Aspermatogenesis in these mutant rats is due to a failure of homologous chromosome synapsis during meiosis.
BRC repeat sequences
DMC1 (DNA meiotic recombinase 1) is a meiosis specific homolog of RAD51 that mediates strand exchange during homologous recombinational repair. DMC1 promotes the formation of DNA strand invasion products (joint molecules) between homologous DNA molecules. Human DMC1 interacts directly with each of a series of repeat sequences in the BRCA2 protein (called BRC repeats) that stimulate joint molecule formation by DMC1.[58] BRC repeats conform to a motif consisting of a sequence of about 35 highly conserved amino acids that are present at least once in all BRCA2-like proteins. The BRCA2 BRC repeats stimulate joint molecule formation by promoting the interaction of single-stranded DNA (ssDNA) with DMC1.[58] The ssDNA complexed with DMC1 can pair with homologous ssDNA from another chromosome during the synapsis stage of meiosis to form a joint molecule, a central step in homologous recombination. Thus the BRC repeat sequences of BRCA2 appear to play a key role in recombinational repair of DNA damages during meiotic recombination.
Overall, it appears that homologous recombination during meiosis functions to repair DNA damages,[59] and that BRCA2 plays a key role in performing this function.
Neurogenesis
BRCA2 is required in the mouse for neurogenesis and suppression of medulloblastoma.[60] ‘’BRCA2’’ loss profoundly affects neurogenesis, particularly during embryonic and postnatal neural development. These neurological defects arise from DNA damage.[60]
Epigenetic control of BRCA2
Epigenetic alterations in expression of BRCA2 (causing over-expression or under-expression) are very frequent in sporadic cancers (see Table below) while mutations in BRCA2 are rarely found.[61][62][63]
In non-small cell lung cancer, BRCA2 is epigenetically repressed by hypermethylation of the promoter.[64] In this case, promoter hypermethylation is significantly associated with low mRNA expression and low protein expression but not with loss of heterozygosity of the gene.
In sporadic ovarian cancer, an opposite effect is found. BRCA2 promoter and 5'-UTR regions have relatively few or no methylated CpG dinucleotides in the tumor DNA compared with that of non-tumor DNA, and a significant correlation is found between hypomethylation and a >3-fold over-expression of BRCA2.[65] This indicates that hypomethylation of the BRCA2 promoter and 5'-UTR regions leads to over-expression of BRCA2 mRNA.
One report indicated some epigenetic control of BRCA2 expression by the microRNAs miR-146a and miR-148a.[66]
BRCA2 expression in cancer
In eukaryotes, BRCA2 protein has an important role in homologous recombinational repair. In mice and humans, BRCA2 primarily mediates orderly assembly of RAD51 on single-stranded (ss) DNA, the form that is active for homologous pairing and strand invasion.[67] BRCA2 also redirects RAD51 from double-stranded DNA and prevents dissociation from ssDNA.[67] In addition, the four paralogs of RAD51, consisting of RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 form a complex called the BCDX2 complex (see Figure: Recombinational repair of DNA). This complex participates in RAD51 recruitment or stabilization at damage sites.[25] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament. RAD51 catalyses strand transfer between a broken sequence and its undamaged homologue to allow re-synthesis of the damaged region (see homologous recombination models).
Some studies of cancers report over-expressed BRCA2 whereas other studies report under-expression of BRCA2. At least two reports found over-expression in some sporadic breast tumors and under-expression in other sporadic breast tumors.[68][69] (see Table).
Many cancers have epigenetic deficiencies in various DNA repair genes (see Frequencies of epimutations in DNA repair genes in cancers). These repair deficiencies likely cause increased unrepaired DNA damages. The over-expression of BRCA2 seen in many cancers may reflect compensatory BRCA2 over-expression and increased homologous recombinational repair to at least partially deal with such excess DNA damages. Egawa et al.[70] suggest that increased expression of BRCA2 can be explained by the genomic instability frequently seen in cancers, which induces BRCA2 mRNA expression due to an increased need of BRCA2 for DNA repair.
Under-expression of BRCA2 would itself lead to increased unrepaired DNA damages. Replication errors past these damages (see translesion synthesis) would lead to increased mutations and cancer.
| Cancer | Over or Under expression | Frequency of altered expression | Evaluation method | Ref. |
|---|---|---|---|---|
| Sporadic ovarian cancer | Over-expression | 80% | messenger RNA | [65] |
| Sporadic ovarian cancer | Under-expression | 42% | immunohistochemistry | [71] |
| (recurrent cancer in study above) | Increased-expression | 71% | immunohistochemistry | [71] |
| Non-small cell lung cancer | Under-expression | 34% | immunohistochemistry | [64] |
| Breast cancer | Over-expression | 66% | messenger RNA | [70] |
| Breast cancer | Over-expression | 20% | messenger RNA | [68] |
| (same study as above) | Under-expression | 11% | messenger RNA | [68] |
| Breast cancer | Over-expression | 30% | immunohistochemistry | [69] |
| (same study as above) | Under-expression | 30% | immunohistochemistry | [69] |
| Triple negative breast cancer | Under-expression | 90% | immunohistochemistry | [72] |
Interactions
BRCA2 has been shown to interact with
- BRE,[73]
- BARD1,[73][74]
- BCCIP,[75]
- BRCA1,[73][76][77][78]
- BRCC3,[73]
- BUB1B,[79]
- CREBBP,[80]
- C11orf30,[81]
- FANCD2,[82][83][84]
- FANCG,[85]
- FLNA,[86]
- HMG20B,[87][88]
- P53,[73][89]
- PALB2,[26][90]
- PCAF,[91][92]
- PLK1,[91][93]
- RAD51,[73][76][91][94][95][96][97][98][99][100][75][77][89]
- RPA1,[101]
- SHFM1[102][103] and
- SMAD3.[104]
Domain architecture
BRCA2 contains a number of 39 amino acid repeats that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment.[89][96][97][105]
The BRCA2 helical domain adopts a helical structure, consisting of a four-helix cluster core (alpha 1, alpha 8, alpha 9, alpha 10) and two successive beta-hairpins (beta 1 to beta 4). An approximately 50-amino acid segment that contains four short helices (alpha 2 to alpha 4), meanders around the surface of the core structure. In BRCA2, the alpha 9 and alpha 10 helices pack with the BRCA2 OB1 domain through van der Waals contacts involving hydrophobic and aromatic residues, and also through side-chain and backbone hydrogen bonds. This domain binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes that map to a 1.5-Mb locus deleted in an inherited developmental malformation syndrome.[103]
The BRCA OB1 domain assumes an OB fold, which consists of a highly curved five-stranded beta-sheet that closes on itself to form a beta-barrel. OB1 has a shallow groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for weak single strand DNA binding. The domain also binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein.[103]
The BRCA OB3 domain assumes an OB fold, which consists of a highly curved five-stranded beta-sheet that closes on itself to form a beta-barrel. OB3 has a pronounced groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for strong ssDNA binding.[103]
The Tower domain adopts a secondary structure consisting of a pair of long, antiparallel alpha-helices (the stem) that support a three-helix bundle (3HB) at their end. The 3HB contains a helix-turn-helix motif and is similar to the DNA binding domains of the bacterial site-specific recombinases, and of eukaryotic Myb and homeodomain transcription factors. The Tower domain has an important role in the tumour suppressor function of BRCA2, and is essential for appropriate binding of BRCA2 to DNA.[103]
Patents, enforcement, litigation, and controversy
Main article: Association for Molecular Pathology v. Myriad Genetics
A patent application for the isolated BRCA1 gene and cancer-cancer promoting mutations, as well as methods to diagnose the likelihood of getting breast cancer, was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics in 1994;[15] over the next year, Myriad, in collaboration with other investigators, isolated and sequenced the BRCA2 gene and identified relevant mutations, and the first BRCA2 patent was filed in the U.S. by Myriad and the other institutions in 1995.[14] Myriad is the exclusive licensee of these patents and has enforced them in the US against clinical diagnostic labs.[18] This business model led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012;[17] it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[18][106] The patents begin to expire in 2014.
According to an article published in the journal, Genetic Medicine, in 2010,[107] "The patent story outside the United States is more complicated.... For example, patents have been obtained but the patents are being ignored by provincial health systems in Canada. In Australia and the UK, Myriad's licensee permitted use by health systems, but announced a change of plans in August 2008. ... Only a single mutation has been patented in Myriad's lone European-wide patent, although some patents remain under review of an opposition proceeding. In effect, the United States is the only jurisdiction where Myriad's strong patent position has conferred sole-provide status."[107][108] Peter Meldrum, CEO of Myriad Genetics, has acknowledged that Myriad has "other competitive advantages that may make such [patent] enforcement unnecessary" in Europe.[109]
Legal decisions surrounding the BRCA1 and BRCA2 patents will affect the field of genetic testing in general.[110] In June 2013, in Association for Molecular Pathology v. Myriad Genetics (No. 12-398), the US Supreme Court unanimously ruled that, "A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated," invalidating Myriad's patents on the BRCA1 and BRCA2 genes. However, the Court also held that manipulation of a gene to create something not found in nature could still be eligible for patent protection.[111] The Federal Court of Australia came to the opposite conclusion, upholding the validity of an Australian Myriad Genetics patent over the BRCA1 gene in February 2013,[112] but this decision is being appealed and the appeal will include consideration of the US Supreme Court ruling.[113]
See also
- BRCA1
- DNA repair
- PALB2
References
- ^ Hamel PJ (2007-05-29). "BRCA1 and BRCA2: No Longer the Only Troublesome Genes Out There". HealthCentral. Retrieved 2010-07-02.
- ^ "OrthoMaM phylogenetic marker: BRCA2 coding sequence".
- ^ Duncan JA, Reeves JR, Cooke TG (October 1998). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular pathology : MP 51 (5): 237–47. doi:10.1136/mp.51.5.237. PMC 395646. PMID 10193517.
- ^ Yoshida K, Miki Y (November 2004). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer science 95 (11): 866–71. doi:10.1111/j.1349-7006.2004.tb02195.x. PMID 15546503.
- ^ Check W (2006-09-01). "BRCA: What we know now". College of American Pathologists. Retrieved 2010-08-23.
- ^ Friedenson B (August 2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers.". BMC Cancer 7: 152–162. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
- ^ Friedenson B (2008-06-08). "Breast cancer genes protect against some leukemias and lymphomas" (video). SciVee.
- ^ "Breast and Ovarian Cancer Genetic Screening". Palo Alto Medical Foundation. Archived from the original on 4 October 2008. Retrieved 2008-10-11.
- ^ Friedenson B (2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer 7: 152. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
- ^ a b Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D (September 1994). "Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13". Science 265 (5181): 2088–90. doi:10.1126/science.8091231. PMID 8091231.
- ^ "BRCA2 breast cancer 2, early onset [Homo sapiens]". EntrezGene. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Breast cancer type 2 susceptibility protein - Homo sapiens (Human)". P51587. UniProt.
- ^ Williams-Jones B (2002). Genetic testing for sale: Implications of commercial brca testing in Canada (Ph.D.). The University of British Columbia.
- ^ a b US patent 5837492, Tavtigian SV, Kamb A, Simard J, Couch F, Rommens JM, Weber BL, "Chromosome 13-linked breast cancer susceptibility gene", issued 1998-11-17, assigned to Myriad Genetics, Inc., Endo Recherche, Inc., HSC Research & Development Limited Partnership, Trustees of the University of Pennsylvania
- ^ a b US patent 5747282, Skolnick HS, Goldgar DE, Miki Y, Swenson J, Kamb A, Harshman KD, Shattuck-Eidens DM, Tavtigian SV, Wiseman RW, Futreal PA, "7Q-linked breast and ovarian cancer susceptibility gene", issued 1998-05-05, assigned to Myriad Genetics, Inc., The United States of America as represented by the Secretary of Health and Human Services, and University of Utah Research Foundation
- ^ US patent 5837492, Tavtigian SV, Kamb A, Simard J, Couch F, Rommens JM, Weber BL, "Chromosome 13-linked breast cancer susceptibility gene", issued 1998-11-17, assigned to Myriad Genetics, Inc., Endo Recherche, Inc., HSC Research & Development Limited Partnership, Trustees of the University of Pennsylvania
- ^ a b Myriad Investor Page—see "Myriad at a glance" accessed October 2012
- ^ a b c Schwartz J (2009-05-12). "Cancer Patients Challenge the Patenting of a Gene". Health. New York Times.
- ^ D'Andrea AD (2010). "Susceptibility pathways in Fanconi's anemia and breast cancer". N. Engl. J. Med. 362 (20): 1909–19. doi:10.1056/NEJMra0809889. PMC 3069698. PMID 20484397.
- ^ Sobeck A, Stone S, Landais I, de Graaf B, Hoatlin ME (2009). "The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways". J. Biol. Chem. 284 (38): 25560–8. doi:10.1074/jbc.M109.007690. PMC 2757957. PMID 19633289.
- ^ Castillo P, Bogliolo M, Surralles J (2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in response to oxidative damage". DNA Repair (Amst.) 10 (5): 518–25. doi:10.1016/j.dnarep.2011.02.007. PMID 21466974.
- ^ Stolz A, Ertych N, Bastians H (2011). "Tumor suppressor CHK2: regulator of DNA damage response and mediator of chromosomal stability". Clin. Cancer Res. 17 (3): 401–5. doi:10.1158/1078-0432.CCR-10-1215. PMID 21088254.
- ^ Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D'Andrea AD (2002). "S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51". Blood 100 (7): 2414–20. doi:10.1182/blood-2002-01-0278. PMID 12239151.
- ^ Park JY, Zhang F, Andreassen PR (2014). "PALB2: the hub of a network of tumor suppressors involved in DNA damage responses". Biochim. Biophys. Acta 1846 (1): 263–75. doi:10.1016/j.bbcan.2014.06.003. PMC 4183126. PMID 24998779.
- ^ a b Chun J, Buechelmaier ES, Powell SN (2013). "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway". Mol. Cell. Biol. 33 (2): 387–95. doi:10.1128/MCB.00465-12. PMC 3554112. PMID 23149936.
- ^ a b Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM (June 2006). "Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2". Mol. Cell 22 (6): 719–29. doi:10.1016/j.molcel.2006.05.022. PMID 16793542.
- ^ Buisson R, Dion-Côté AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY (2010). "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.". Nature Structural & Molecular Biology 17 (10): 1247–54. doi:10.1038/nsmb.1915. PMID 20871615.
- ^ Levin B, Lech D, Friedenson B (2012). "Evidence that BRCA1- or BRCA2-associated cancers are not inevitable". Molecular Medicine 18: 1327–37. doi:10.2119/molmed.2012.00280. PMC 3521784. PMID 22972572.
- ^ "High-Penetrance Breast and/or Ovarian Cancer Susceptibility Genes". National Cancer Institute. Retrieved 7 December 2012.
- ^ Strattot, M. (1995). "Identification of the breast cancer susceptibility gene BRCA2". Nature 378 (21): 789–791. doi:10.1038/378789a0. PMID 11902570.
- ^ High-Impact Science: Tracking down the BRCA genes (Part 2) - Cancer Research UK science blog, 2012
- ^ Route information board
- ^ a b Lacroix M, Leclercq G (2005). "The "portrait" of hereditary breast cancer". Breast Cancer Research and Treatment 89 (3): 297–304. doi:10.1007/s10549-004-2172-4. PMID 15754129.
- ^ a b Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, Tulinius H, Ogmundsdottir HM, Eyfjörd JE (1996). "A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes". Nature Genetics 13 (1): 117–119. doi:10.1038/ng0596-117. PMID 8673089.
- ^ a b Thorlacius S, Sigurdsson S, Bjarnadottir H, Olafsdottir G, Jonasson JG, Tryggvadottir L, Tulinius H, Eyfjörd JE (1997). "Study of a single BRCA2 mutation with high carrier frequency in a small population". American Journal of Human Genetics 60 (5): 1079–1085. PMC 1712443. PMID 9150155.
- ^ den Dunnen JT, Antonarakis SE (2000). "Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion.". Human Mutation 15 (1): 7–12. doi:10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N. PMID 10612815.
- ^ Neuhausen S, Gilewski T, Norton L, Tran T, McGuire P, Swensen J, Hampel H, Borgen P, Brown K, Skolnick M, Shattuck-Eidens D, Jhanwar S, Goldgar D, Offit K (1996). "Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer". Nature Genetics 13 (1): 126–128. doi:10.1038/ng0596-126. PMID 8673092.
- ^ Verhoog LC, van den Ouweland AM, Berns E, van Veghel-Plandsoen MM, van Staveren IL, Wagner A, Bartels CC, Tilanus-Linthorst MM, Devilee P, Seynaeve C, Halley DJ, Niermeijer MF, Klijn JG, Meijers-Heijboer H (2001). "Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families". European Journal of Cancer 37 (16): 2082–2090. doi:10.1016/S0959-8049(01)00244-1. PMID 11597388.
- ^ Huusko P, Pääkkönen K, Launonen V, Pöyhönen M, Blanco G, Kauppila A, Puistola U, Kiviniemi H, Kujala M, Leisti J, Winqvist R (1998). "Evidence of founder mutations in Finnish BRCA1 and BRCA2 families". American Journal of Human Genetics 62 (6): 1544–1548. doi:10.1086/301880. PMC 1377159. PMID 9585608.
- ^ Pääkkönen K, Sauramo S, Sarantaus L, Vahteristo P, Hartikainen A, Vehmanen P, Ignatius J, Ollikainen V, Kääriäinen H, Vauramo E, Nevanlinna H, Krahe R, Holli K, Kere J (2001). "Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population". Genetic Epidemiology 20 (2): 239–246. doi:10.1002/1098-2272(200102)20:2<239::AID-GEPI6>3.0.CO;2-Y. PMID 11180449.
- ^ Tonin PN, Mes-Masson AM, Narod SA, Ghadirian P, Provencher D (1999). "Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history". Clinical Genetics 55 (5): 318–324. doi:10.1034/j.1399-0004.1999.550504.x. PMID 10422801.
- ^ Oros KK, Leblanc G, Arcand SL, Shen Z, Perret C, Mes-Masson AM, Foulkes WD, Ghadirian P, Provencher D, Tonin PN (2006). "Haplotype analysis suggests common founders in carriers of recurrent BRCA2 mutation, 3398delAAAAG, in French Canadian hereditary breast and/ovarian cancer families". BMC Medical Genetics 7 (23). doi:10.1186/1471-2350-7-23. PMID 16539696.
- ^ Tonin PN (2006). "The limited spectrum of pathogenic BRCA1 and BRCA2 mutations in the French Canadian breast and breast-ovarian cancer families, a founder population of Quebec, Canada". Bull Cancer 93 (9): 841–846. PMID 16980226.
- ^ Van Der Looij M, Szabo C, Besznyak I, Liszka G, Csokay B, Pulay T, Toth J, Devilee P, King MC, Olah E (2000). "Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary". International Journal of Cancer 86 (5): 737–740. doi:10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1. PMID 10797299.
- ^ Pisano M, Cossu A, Persico I, Palmieri G, Angius A, Casu G, Palomba G, Sarobba MG, Rocca PC, Dedola MF, Olmeo N, Pasca A, Budroni M, Marras V, Pisano A, Farris A, Massarelli G, Pirastu M, Tanda F (2000). "Identification of a founder BRCA2 mutation in Sardinia". British Journal of Cancer 82 (3): 553–559. doi:10.1054/bjoc.1999.0963. PMC 2363305. PMID 10682665.
- ^ a b Scottish/Northern Irish BRCAI/BRCA2 Consortium (2003). "BRCA1 and BRCA2 mutations in Scotland and Northern Ireland". British Journal of Cancer 88 (8): 1256–1262. doi:10.1038/sj.bjc.6600840. PMC 2747571. PMID 12698193.
- ^ Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA (2002). "Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan". American Journal of Human Genetics 71 (3): 595–606. doi:10.1086/342506. PMC 379195. PMID 12181777.
- ^ Krajc M, De Grève J, Goelen G, Teugels E (2002). "BRCA2 founder mutation in Slovenian breast cancer families". European Journal of Human Genetics 10 (12): 879–882. doi:10.1038/sj.ejhg.5200886. PMID 12461697.
- ^ Osorio A, Barroso A, Martínez B, Cebrián A, San Román JM, Lobo F, Robledo M, Benítez J (1998). "Molecular analysis of the BRCA2 gene in 16 breast/ovarian cancer Spanish families". Clinical Genetics 54 (7): 142–147. doi:10.1054/bjoc.1999.1089. PMC 2374482. PMID 10755399.
- ^ Neuhausen SL (2000). "Founder populations and their uses for breast cancer genetics". Cancer Research 2 (2): 77–81. doi:10.1186/bcr36. PMC 139426. PMID 11250694.
- ^ a b Seeliger K, Dukowic-Schulze S, Wurz-Wildersinn R, Pacher M, Puchta H (2012). "BRCA2 is a mediator of RAD51- and DMC1-facilitated homologous recombination in Arabidopsis thaliana". New Phytol. 193 (2): 364–75. doi:10.1111/j.1469-8137.2011.03947.x. PMID 22077663.
- ^ Kojic M, Kostrub CF, Buchman AR, Holloman WK (2002). "BRCA2 homolog required for proficiency in DNA repair, recombination, and genome stability in Ustilago maydis". Mol. Cell 10 (3): 683–91. PMID 12408834.
- ^ Ko E, Lee J, Lee H (2008). "Essential role of brc-2 in chromosome integrity of germ cells in C. elegans". Mol. Cells 26 (6): 590–4. PMID 18779660.
- ^ Martin JS, Winkelmann N, Petalcorin MI, McIlwraith MJ, Boulton SJ (2005). "RAD-51-dependent and -independent roles of a Caenorhabditis elegans BRCA2-related protein during DNA double-strand break repair". Mol. Cell. Biol. 25 (8): 3127–39. doi:10.1128/MCB.25.8.3127-3139.2005. PMC 1069622. PMID 15798199.
- ^ Klovstad M, Abdu U, Schüpbach T (2008). "Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint". PLoS Genet. 4 (2): e31. doi:10.1371/journal.pgen.0040031. PMC 2233675. PMID 18266476.
- ^ Connor F, Bertwistle D, Mee PJ, Ross GM, Swift S, Grigorieva E, Tybulewicz VL, Ashworth A (1997). "Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation". Nat. Genet. 17 (4): 423–30. doi:10.1038/ng1297-423. PMID 9398843.
- ^ Cotroneo MS, Haag JD, Zan Y, Lopez CC, Thuwajit P, Petukhova GV, Camerini-Otero RD, Gendron-Fitzpatrick A, Griep AE, Murphy CJ, Dubielzig RR, Gould MN (2007). "Characterizing a rat Brca2 knockout model". Oncogene 26 (11): 1626–35. doi:10.1038/sj.onc.1209960. PMID 16964288.
- ^ a b Martinez JS, von Nicolai C, Kim T, Ehlén Å, Mazin AV, Kowalczykowski SC, Carreira A (2016). "BRCA2 regulates DMC1-mediated recombination through the BRC repeats". Proc. Natl. Acad. Sci. U.S.A. 113 (13): 3515–20. doi:10.1073/pnas.1601691113. PMC 4822569. PMID 26976601.
- ^ Bernstein H and Bernstein C (2013). Evolutionary Origin and Adaptive Function of Meiosis. In Meiosis: Bernstein C and Bernstein H, editors. ISBN 978-953-51-1197-9, InTech, http://www.intechopen.com/books/meiosis/evolutionary-origin-and-adaptive-function-of-meiosis
- ^ a b Frappart PO, Lee Y, Lamont J, McKinnon PJ (2007). "BRCA2 is required for neurogenesis and suppression of medulloblastoma". EMBO J. 26 (11): 2732–42. doi:10.1038/sj.emboj.7601703. PMC 1888666. PMID 17476307.
- ^ Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, Davis T, Ha PC, Kehrer R, Jammulapati S, Chen Q, Offit K, Skolnick MH, Tavtigian SV, Jhanwar S, Swedlund B, Wong AK, Kamb A (1996). "Low incidence of BRCA2 mutations in breast carcinoma and other cancers". Nat. Genet. 13 (2): 241–4. doi:10.1038/ng0696-241. PMID 8640236.
- ^ Miki Y, Katagiri T, Kasumi F, Yoshimoto T, Nakamura Y (1996). "Mutation analysis in the BRCA2 gene in primary breast cancers". Nat. Genet. 13 (2): 245–7. doi:10.1038/ng0696-245. PMID 8640237.
- ^ Lancaster JM, Wooster R, Mangion J, Phelan CM, Cochran C, Gumbs C, Seal S, Barfoot R, Collins N, Bignell G, Patel S, Hamoudi R, Larsson C, Wiseman RW, Berchuck A, Iglehart JD, Marks JR, Ashworth A, Stratton MR, Futreal PA (1996). "BRCA2 mutations in primary breast and ovarian cancers". Nat. Genet. 13 (2): 238–40. doi:10.1038/ng0696-238. PMID 8640235.
- ^ a b Lee MN, Tseng RC, Hsu HS, Chen JY, Tzao C, Ho WL, Wang YC (2007). "Epigenetic inactivation of the chromosomal stability control genes BRCA1, BRCA2, and XRCC5 in non-small cell lung cancer". Clin. Cancer Res. 13 (3): 832–8. doi:10.1158/1078-0432.CCR-05-2694. PMID 17289874.
- ^ a b Chan KY, Ozçelik H, Cheung AN, Ngan HY, Khoo US (2002). "Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer". Cancer Res. 62 (14): 4151–6. PMID 12124354.
- ^ Gu Y, Zhang M, Peng F, Fang L, Zhang Y, Liang H, Zhou W, Ao L, Guo Z (2015). "The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2". Oncotarget 6 (4): 2397–406. doi:10.18632/oncotarget.2963. PMC 4385859. PMID 25537514.
- ^ a b Holloman WK (2011). "Unraveling the mechanism of BRCA2 in homologous recombination". Nat. Struct. Mol. Biol. 18 (7): 748–54. doi:10.1038/nsmb.2096. PMC 3647347. PMID 21731065.
- ^ a b c Bièche I, Noguès C, Lidereau R (1999). "Overexpression of BRCA2 gene in sporadic breast tumours". Oncogene 18 (37): 5232–8. doi:10.1038/sj.onc.1202903. PMID 10498873.
- ^ a b c Hedau S, Batra M, Singh UR, Bharti AC, Ray A, Das BC (2015). "Expression of BRCA1 and BRCA2 proteins and their correlation with clinical staging in breast cancer". J Cancer Res Ther 11 (1): 158–63. doi:10.4103/0973-1482.140985. PMID 25879355.
- ^ a b Egawa C, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S (2002). "High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients". Int. J. Cancer 98 (6): 879–82. PMID 11948466.
- ^ a b Swisher EM, Gonzalez RM, Taniguchi T, Garcia RL, Walsh T, Goff BA, Welcsh P (2009). "Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas". Mol. Cancer 8: 48. doi:10.1186/1476-4598-8-48. PMC 2719582. PMID 19602291.
- ^ Thike AA, Tan PH, Ikeda M, Iqbal J (2016). "Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple-negative breast cancer, adversely affects survival". Histopathology 68 (5): 702–12. doi:10.1111/his.12801. PMID 26259780.
- ^ a b c d e f Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R (November 2003). "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair". Mol. Cell 12 (5): 1087–99. doi:10.1016/S1097-2765(03)00424-6. PMID 14636569.
- ^ Ryser S, Dizin E, Jefford CE, Delaval B, Gagos S, Christodoulidou A, Krause KH, Birnbaum D, Irminger-Finger I (February 2009). "Distinct roles of BARD1 isoforms in mitosis: full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Res. 69 (3): 1125–34. doi:10.1158/0008-5472.CAN-08-2134. PMID 19176389.
- ^ a b Liu J, Yuan Y, Huan J, Shen Z (January 2001). "Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2". Oncogene 20 (3): 336–45. doi:10.1038/sj.onc.1204098. PMID 11313963.
- ^ a b Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA (October 2001). "Analysis of murine Brca2 reveals conservation of protein-protein interactions but differences in nuclear localization signals". J. Biol. Chem. 276 (40): 37640–8. doi:10.1074/jbc.M106281200. PMID 11477095.
- ^ a b Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R (September 1998). "Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells". Mol. Cell 2 (3): 317–28. doi:10.1016/S1097-2765(00)80276-2. PMID 9774970.
- ^ Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
- ^ Futamura M, Arakawa H, Matsuda K, Katagiri T, Saji S, Miki Y, Nakamura Y (March 2000). "Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1". Cancer Res. 60 (6): 1531–5. PMID 10749118.
- ^ Siddique H, Rao VN, Reddy ES (August 2009). "CBP-mediated post-translational N-glycosylation of BRCA2". Int J Oncol. 35 (2): 16387–91. doi:10.3892/ijo_00000351. PMID 19578754.
- ^ Hughes-Davies L, Huntsman D, Ruas M, Fuks F, Bye J, Chin SF, Milner J, Brown LA, Hsu F, Gilks B, Nielsen T, Schulzer M, Chia S, Ragaz J, Cahn A, Linger L, Ozdag H, Cattaneo E, Jordanova ES, Schuuring E, Yu DS, Venkitaraman A, Ponder B, Doherty A, Aparicio S, Bentley D, Theillet C, Ponting CP, Caldas C, Kouzarides T (November 2003). "EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer". Cell 115 (5): 523–35. doi:10.1016/S0092-8674(03)00930-9. PMID 14651845.
- ^ Wang X, Andreassen PR, D'Andrea AD (July 2004). "Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin". Mol. Cell. Biol. 24 (13): 5850–62. doi:10.1128/MCB.24.13.5850-5862.2004. PMC 480901. PMID 15199141.
- ^ Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG (June 2004). "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways". Hum. Mol. Genet. 13 (12): 1241–8. doi:10.1093/hmg/ddh135. PMID 15115758.
- ^ Hejna J, Holtorf M, Hines J, Mathewson L, Hemphill A, Al-Dhalimy M, Olson SB, Moses RE (April 2008). "Tip60 is required for DNA interstrand cross-link repair in the Fanconi anemia pathway". J. Biol. Chem. 283 (15): 9844–51. doi:10.1074/jbc.M709076200. PMC 2398728. PMID 18263878.
- ^ Hussain S, Witt E, Huber PA, Medhurst AL, Ashworth A, Mathew CG (October 2003). "Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1". Hum. Mol. Genet. 12 (19): 2503–10. doi:10.1093/hmg/ddg266. PMID 12915460.
- ^ Yuan Y, Shen Z (December 2001). "Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response". J. Biol. Chem. 276 (51): 48318–24. doi:10.1074/jbc.M102557200. PMID 11602572.
- ^ Marmorstein LY, Kinev AV, Chan GK, Bochar DA, Beniya H, Epstein JA, Yen TJ, Shiekhattar R (January 2001). "A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression". Cell 104 (2): 247–57. doi:10.1016/S0092-8674(01)00209-4. PMID 11207365.
- ^ Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R (May 2002). "A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7420–5. doi:10.1073/pnas.112008599. PMC 124246. PMID 12032298.
- ^ a b c Marmorstein LY, Ouchi T, Aaronson SA (November 1998). "The BRCA2 gene product functionally interacts with p53 and RAD51". Proc. Natl. Acad. Sci. U.S.A. 95 (23): 13869–74. doi:10.1073/pnas.95.23.13869. PMC 24938. PMID 9811893.
- ^ "Entrez Gene: PALB2 partner and localizer of BRCA2".
- ^ a b c Lin HR, Ting NS, Qin J, Lee WH (September 2003). "M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex". J. Biol. Chem. 278 (38): 35979–87. doi:10.1074/jbc.M210659200. PMID 12815053.
- ^ Fuks F, Milner J, Kouzarides T (November 1998). "BRCA2 associates with acetyltransferase activity when bound to P/CAF". Oncogene 17 (19): 2531–4. doi:10.1038/sj.onc.1202475. PMID 9824164.
- ^ Lee M, Daniels MJ, Venkitaraman AR (January 2004). "Phosphorylation of BRCA2 by the Polo-like kinase Plk1 is regulated by DNA damage and mitotic progression". Oncogene 23 (4): 865–72. doi:10.1038/sj.onc.1207223. PMID 14647413.
- ^ Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele G, Hasty P, Bradley A (April 1997). "Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2". Nature 386 (6627): 804–10. doi:10.1038/386804a0. PMID 9126738.
- ^ Yu DS, Sonoda E, Takeda S, Huang CL, Pellegrini L, Blundell TL, Venkitaraman AR (October 2003). "Dynamic control of Rad51 recombinase by self-association and interaction with BRCA2". Mol. Cell 12 (4): 1029–41. doi:10.1016/S1097-2765(03)00394-0. PMID 14580352.
- ^ a b Chen PL, Chen CF, Chen Y, Xiao J, Sharp ZD, Lee WH (April 1998). "The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment". Proc. Natl. Acad. Sci. U.S.A. 95 (9): 5287–92. doi:10.1073/pnas.95.9.5287. PMC 20253. PMID 9560268.
- ^ a b Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL (December 1997). "RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2". J. Biol. Chem. 272 (51): 31941–4. doi:10.1074/jbc.272.51.31941. PMID 9405383.
- ^ Katagiri T, Saito H, Shinohara A, Ogawa H, Kamada N, Nakamura Y, Miki Y (March 1998). "Multiple possible sites of BRCA2 interacting with DNA repair protein RAD51". Genes Chromosomes Cancer 21 (3): 217–22. doi:10.1002/(SICI)1098-2264(199803)21:3<217::AID-GCC5>3.0.CO;2-2. PMID 9523196.
- ^ Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR (November 2002). "Insights into DNA recombination from the structure of a RAD51-BRCA2 complex". Nature 420 (6913): 287–93. doi:10.1038/nature01230. PMID 12442171.
- ^ Tarsounas M, Davies AA, West SC (January 2004). "RAD51 localization and activation following DNA damage". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 359 (1441): 87–93. doi:10.1098/rstb.2003.1368. PMC 1693300. PMID 15065660.
- ^ Wong JM, Ionescu D, Ingles CJ (January 2003). "Interaction between BRCA2 and replication protein A is compromised by a cancer-predisposing mutation in BRCA2". Oncogene 22 (1): 28–33. doi:10.1038/sj.onc.1206071. PMID 12527904.
- ^ Marston NJ, Richards WJ, Hughes D, Bertwistle D, Marshall CJ, Ashworth A (July 1999). "Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals". Mol. Cell. Biol. 19 (7): 4633–42. PMC 84261. PMID 10373512.
- ^ a b c d e Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH, Pavletich NP (September 2002). "BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure". Science 297 (5588): 1837–48. doi:10.1126/science.297.5588.1837. PMID 12228710.
- ^ Preobrazhenska O, Yakymovych M, Kanamoto T, Yakymovych I, Stoika R, Heldin CH, Souchelnytskyi S (August 2002). "BRCA2 and Smad3 synergize in regulation of gene transcription". Oncogene 21 (36): 5660–4. doi:10.1038/sj.onc.1205732. PMID 12165866.
- ^ Bork P, Blomberg N, Nilges M (May 1996). "Internal repeats in the BRCA2 protein sequence". Nat. Genet. 13 (1): 22–3. doi:10.1038/ng0596-22. PMID 8673099.
- ^ "ACLU sues over patents on breast cancer genes". CNN. Archived from the original on 15 May 2009. Retrieved 2009-05-14.
- ^ a b Cook-Deegan, R; Derienzo, C; Carbone, J; Chandrasekharan, S; Heaney, C; Conover, C (2010). "Impact of gene patents and licensing practices on access to genetic testing for inherited susceptibility to cancer: Comparing breast and ovarian cancers with colon cancers". Genetics in Medicine 12 (4 Suppl): S15–38. doi:10.1097/GIM.0b013e3181d5a67b. PMC 3047448. PMID 20393305.
- ^ Benowitz S (January 2003). "European groups oppose Myriad's latest patent on BRCA1". J. Natl. Cancer Inst. 95 (1): 8–9. doi:10.1093/jnci/95.1.8. PMID 12509391.
- ^ Conley J, Vorhous D, Cook-Deegan J (2011-03-01). "How Will Myriad Respond to the Next Generation of BRCA Testing?". Robinson, Bradshaw, and Hinson. Retrieved 2012-12-09.
- ^ "Genetics and Patenting". Human Genome Project Information. U.S. Department of Energy Genome Programs. 2010-07-07.
- ^ Liptak, Adam (13 June 2013). "Supreme Court Rules Human Genes May Not Be Patented". New York Times. Retrieved 13 June 2013.
- ^ Corderoy, Amy (February 15, 2013). "Landmark patent ruling over breast cancer gene BRCA1". Sydney Morning Herald. Retrieved June 14, 2013.
- ^ Corderoy, Amy (June 14, 2013). "Companies can't patent genes, US court rules". Sydney Morning Herald. Retrieved June 14, 2013.
Further reading
- Zou JP, Hirose Y, Siddique H, Rao VN, Reddy ES (1999). "Structure and expression of variant BRCA2a lacking the transactivation domain". Oncology Reports 6 (2): 437–40. doi:10.3892/or.6.2.437. PMID 10023017.
- Venkitaraman AR (2001). "Chromosome stability, DNA recombination and the BRCA2 tumour suppressor". Current Opinion in Cell Biology 13 (3): 338–43. doi:10.1016/S0955-0674(00)00217-9. PMID 11343905.
- Orelli BJ, Bishop DK (2001). "BRCA2 and homologous recombination". Breast Cancer Research 3 (5): 294–8. doi:10.1186/bcr310. PMC 138691. PMID 11597317.
- Daniel DC (2002). "Highlight: BRCA1 and BRCA2 proteins in breast cancer". Microscopy Research and Technique 59 (1): 68–83. doi:10.1002/jemt.10178. PMID 12242698.
- Tutt A, Ashworth A (2003). "The relationship between the roles of BRCA genes in DNA repair and cancer predisposition". Trends in Molecular Medicine 8 (12): 571–6. doi:10.1016/S1471-4914(02)02434-6. PMID 12470990.
- Gonçalves A, Viens P, Sobol H, Maraninchi D, Bertucci F (2005). "[Molecular alterations in breast cancer: clinical implications and new analytical tools]". Revue de Médecine Interne 26 (6): 470–8. doi:10.1016/j.revmed.2004.11.012. PMID 15936476.
- Hay T, Clarke AR (2005). "DNA damage hypersensitivity in cells lacking BRCA2: a review of in vitro and in vivo data". Biochemical Society Transactions 33 (Pt 4): 715–7. doi:10.1042/BST0330715. PMID 16042582.
- Domchek SM, Weber BL (2006). "Clinical management of BRCA1 and BRCA2 mutation carriers". Oncogene 25 (43): 5825–31. doi:10.1038/sj.onc.1209881. PMID 16998496.
- Honrado E, Osorio A, Palacios J, Benitez J (2006). "Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations". Oncogene 25 (43): 5837–45. doi:10.1038/sj.onc.1209875. PMID 16998498.
External links
- BRCA2 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NCBI/NIH/UW entry on BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer
- OMIM entries on BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer
- EntrezGene 675
- GeneCard
- Cancer.gov
- "FORCE: Facing Our Risk of Cancer Empowered -- Hereditary, Genetic Breast or Ovarian Cancer and BRCA Issues". Facing Our Risk of Cancer Empowered, Inc. Archived from the original on 29 September 2008. Retrieved 2008-10-11.
- UCSC Genome Browser View
- den Dunnen JT, Antonarakis SE (2000). "Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion". Human Mutation 15 (1): 7–12. doi:10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N. PMID 10612815.
- UCSC Gene details page
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This article incorporates text from the public domain Pfam and InterPro IPR002093
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UpToDate Contents
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- 1. BRCA1 and BRCA2: Prevalence and risks for breast and ovarian cancer
- 2. 遺伝性乳癌・卵巣癌症候群およびBRCA変異を持つ患者のマネージメント management of hereditary breast and ovarian cancer syndrome and patients with brca mutations
- 3. 上皮性卵巣癌、卵管癌、および腹膜癌：疫学および危険因子 epithelial carcinoma of the ovary fallopian tube and peritoneum epidemiology and risk factors
- 4. 遺伝性乳癌・卵巣癌症候群の遺伝子検査 genetic testing for hereditary breast and ovarian cancer syndrome
- 5. 子宮摘出時の選択的卵巣摘出術または卵巣保全 elective oophorectomy or ovarian conservation at the time of hysterectomy
English Journal
- RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis.
- Yang G, Mercado-Uribe I, Multani AS, Sen S, Shih IeM, Wong KK, Gershenson DM, Liu J.SourceCancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
- International journal of cancer. Journal international du cancer.Int J Cancer.2013 Jul 15;133(2):275-85. doi: 10.1002/ijc.28032. Epub 2013 Feb 12.
- The oncogene RAS is known to induce genomic instability, leading to cancer development; the underlying mechanism, however, remains poorly understood. To better understand how RAS functions, we measured the activity of the functionally related genes Aurora-A and BRCA2 in ovarian cancer cell lines and
- PMID 23319376
- Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation.
- Senst N, Llacuachaqui M, Lubinski J, Lynch H, Armel S, Neuhausen S, Ghadirian P, Sun P, Narod S; Hereditary Breast Cancer Study Group.SourceWomen's College Research Institute, Toronto, Ontario, Canada.
- Clinical genetics.Clin Genet.2013 Jul;84(1):43-6. doi: 10.1111/cge.12037. Epub 2012 Nov 7.
- The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast
- PMID 23066998
Japanese Journal
- The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination.
- Qing Yong,Yamazoe Mitsuyoshi,Hirota Kouji,Dejsuphong Donniphat,Sakai Wataru,Yamamoto Kimiyo N,Bishop Douglas K,Wu XiaoHua,Takeda Shunichi
- PLoS genetics 7(7), 2011-07
- … The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. … We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. … We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. …
- NAID 120003338841
Related Links
- BRCA2とは？goo Wikipedia (ウィキペディア) 。出典：Wikipedia（ウィキペディア）フリー百科事典。 BRCA2とは - goo Wikipedia (ウィキペディア) gooトップ サイトマップ スタートページに設定 RSS ヘルプ メニューへスキップ 本文へスキップ ...
- キーポイント ・BRCA1およびBRCA2は腫瘍抑制遺伝子として知られる遺伝子のクラスに属するヒト遺伝子です。これらの遺伝子の変異は、遺伝性乳癌および卵巣癌と関連しています（Question 1参照）。 ・悪影響を及ぼす(有害な)BRCA1またはBRCA2 ...
Related Pictures
★リンクテーブル★
| リンク元 | 「癌」「癌抑制遺伝子」 |
「癌」
種類
- 癌腫(carcinoma):上皮性
- 肉腫(sarcoma):間葉系
- carcinoma：腺癌(adenocarcinma)、扁平上皮癌(squamous cell carcinoma)、移行上皮癌(transitional cell carcinoma)
- sarcoma：骨肉腫、横紋筋肉腫、平滑筋肉腫、脂肪肉腫、線維肉腫
| Neoplasm | Causes | Effect |
| Small cell lung carcinoma | ACTH or ACTH-like peptide | Cushing’s syndrome |
| Small cell lung carcinoma and intracranial neoplasms | ADH | SIADH |
| Squamous cell lung carcinoma, renal cell carcinoma, breast carcinoma, multiple myeloma, and bone metastasis (lysed bone) | PTH-related peptide, TGF-β, TNF-α, IL-1 | Hypercalcemia |
| Renal cell carcinoma, hemangioblastoma | Erythropoietin | Polycythemia |
| Thymoma, small cell lung carcinoma | Antibodies against presynaptic Ca2+ channels at neuromuscular junction | Lambert-Eaton syndrome (muscle weakness) |
| Leukemias and lymphomas | Hyperuricemia due to excess nucleic acid turnover (i.e., cytotoxic therapy) | Gout, urate nephropathy |
- 最新癌統計
| ●2005年の死亡数が多い部位は順に | ||||||
| 1位 | 2位 | 3位 | 4位 | 5位 | ||
| 男性 | 肺 | 胃 | 肝臓 | 結腸 | 膵臓 | 結腸と直腸を合わせた大腸は4位 |
| 女性 | 胃 | 肺 | 結腸 | 肝臓 | 乳房 | 結腸と直腸を合わせた大腸は1位 |
| 男女計 | 肺 | 胃 | 肝臓 | 結腸 | 膵臓 | 結腸と直腸を合わせた大腸は3位 |
| ●2001年の罹患数が多い部位は順に | ||||||
| 1位 | 2位 | 3位 | 4位 | 5位 | ||
| 男性 | 胃 | 肺 | 結腸 | 肝臓 | 前立腺 | 結腸と直腸を合わせた大腸は2位 |
| 女性 | 乳房*1 | 胃 | 結腸 | 子宮*1 | 肺 | 結腸と直腸を合わせた大腸は1位 |
| 男女計 | 胃 | 肺 | 結腸 | 乳房*1 | 肝臓 | 結腸と直腸を合わせた大腸は2位 |
| *1上皮内がんを含む。 | ||||||
癌の素因となる遺伝子
- HIM.494
| Table 79-1 Cancer Predisposition Syndromes and Associated Genes | ||||
| Syndrome | Gene | Chromosome | Inheritance | Tumors |
| ataxia telangiectasia | ATM | 11q22-q23 | AR | breast cancer |
| autoimmune lymphoproliferative syndrome | FAS | 10q24 | AD | lymphomas |
| FASL | 1q23 | |||
| Bloom syndrome | BLM | 15q26.1 | AR | cancer of all types |
| Cowden syndrome | PTEN | 10q23 | AD | breast, thyroid |
| familial adenomatous polyposis | APC | 5q21 | AD | intestinal adenoma, colorectal cancer |
| familial melanoma | p16INK4 | 9p21 | AD | melanoma, pancreatic cancer |
| familial Wilms tumor | WT1 | 11p13 | AD | pediatric kidney cancer |
| hereditary breast/ovarian cancer | BRCA1 | 17q21 | AD | breast, ovarian, colon, prostate |
| BRCA2 | 13q12.3 | |||
| hereditary diffuse gastric cancer | CDH1 | 16q22 | AD | stomach cancers |
| hereditary multiple exostoses | EXT1 | 8q24 | AD | exostoses, chondrosarcoma |
| EXT2 | 11p11-12 | |||
| hereditary prostate cancer | HPC1 | 1q24-25 | AD | prostate carcinoma |
| hereditary retinoblastoma | RB1 | 13q14.2 | AD | retinoblastoma, osteosarcoma |
| hereditary nonpolyposis colon cancer (HNPCC) | MSH2 | 2p16 | AD | colon, endometrial, ovarian, stomach, small bowel, ureter carcinoma |
| MLH1 | 3p21.3 | |||
| MSH6 | 2p16 | |||
| PMS2 | 7p22 | |||
| hereditary papillary renal carcinoma | MET | 7q31 | AD | papillary renal tumor |
| juvenile polyposis | SMAD4 | 18q21 | AD | gastrointestinal, pancreatic cancers |
| Li-Fraumeni | TP53 | 17p13.1 | AD | sarcoma, breast cancer |
| multiple endocrine neoplasia type 1 | MEN1 | 11q13 | AD | parathyroid, endocrine, pancreas, and pituitary |
| multiple endocrine neoplasia type 2a | RET | 10q11.2 | AD | medullary thyroid carcinoma, pheochromocytoma |
| neurofibromatosis type 1 | NF1 | 17q11.2 | AD | neurofibroma, neurofibrosarcoma, brain tumor |
| neurofibromatosis type 2 | NF2 | 22q12.2 | AD | vestibular schwannoma, meningioma, spine |
| nevoid basal cell carcinoma syndrome (Gorlin's syndrome) | PTCH | 9q22.3 | AD | basal cell carcinoma, medulloblastoma, jaw cysts |
| tuberous sclerosis | TSC1 | 9q34 | AD | angiofibroma, renal angiomyolipoma |
| TSC2 | 16p13.3 | |||
| von Hippel–Lindau | VHL | 3p25-26 | AD | kidney, cerebellum, pheochromocytoma |
癌の危険因子
| 疾患 | 危険因子 | 防御因子 | |
| 悪性腫瘍 | 胃癌 | 塩辛い食品、喫煙、くん製製品、ニトロソアミン土壌、腸上皮化生、Helicobacter pyroli | ビタミンC、野菜、果実 |
| 食道癌 | 喫煙、飲酒、熱い飲食物 | 野菜、果実 | |
| 結腸癌 | 高脂肪食、肉食、低い身体活動、腸内細菌叢の変化、遺伝(家族性大腸腺腫症) | ||
| 肝癌 | HBVキャリア・HCVキャリア、アフラトキシン、住血吸虫、飲酒 | ||
| 肺癌 | 喫煙(特に扁平上皮癌)、大気汚染、職業的暴露(石綿(扁平上皮癌、悪性中皮腫)、クロム) | 野菜、果実 | |
| 膵癌 | 高脂肪食、喫煙 | ||
| 口腔癌 | 喫煙(口唇・舌-パイプ)、ビンロウ樹の実(口腔、舌)、飲酒 | ||
| 咽頭癌 | EBウイルス(上咽頭癌)、飲酒 | ||
| 喉頭癌 | 喫煙、男性、アルコール | ||
| 乳癌 | 高年初産、乳癌の家族歴、肥満、未婚で妊娠回数少ない、無授乳、脂肪の過剰摂取、低年齢初経、高年齢閉経 | 母乳授乳 | |
| 子宮頚癌 | 初交年齢若い、早婚、多産、性交回数が多い(売春)、貧困、不潔]、HSV-2、HPV、流産、人工妊娠中絶回数が多い | ||
| 子宮体癌 | 肥満、糖尿病、ピル、エストロゲン常用、未婚、妊娠回数少ない、乳癌後のタモキシフエン内服 | ||
| 膀胱癌 | 喫煙、鎮痛剤乱用、ビルハルツ住血吸虫、サッカリン、防腐剤 | ||
| 皮膚癌 | 日光(紫外線)、ヒ素(Bowen病) | ||
| 白血病 | 放射線、ベンゼン、地域集積性(ATL)、ダウン症(小児白血病) | ||
| 骨腫瘍 | 電離放射線 | ||
| 甲状腺癌 | ヨード欠乏または過剰 | ||
「癌抑制遺伝子」
- 英
- tumor suppressor gene, tumor suppressor genes, suppressor oncogene, anti-oncogene
- 同
- がん抑制遺伝子、腫瘍抑制遺伝子
- 関
- 癌遺伝子