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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/12 16:33:49」(JST)

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DNA mismatch repair protein Msh2 also known as MutS protein homolog 2 or MSH2 is a protein that in humans is encoded by the MSH2 gene, which is located on chromosome 2. MSH2 is a tumor suppressor gene and more specifically a caretaker gene that codes for a DNA mismatch repair (MMR) protein, MSH2 which forms a heterodimer with MSH6 to make the human MutSα mismatch repair complex. It also dimerizes with MSH3 to form the MutSβ DNA repair complex. MSH2 is involved in many different forms of DNA repair, including transcription-coupled repair,^[1] homologous recombination,^[2] and base excision repair.^[3]

Mutations in the MSH2 gene are associated with microsatellite instability and some cancers, especially with hereditary nonpolyposis colorectal cancer (HNPCC).

Clinical significance

Hereditary nonpolyposis colorectal cancer (HNPCC), sometimes referred to as Lynch syndrome, is inherited in an autosomal dominant fashion, where inheritance of only one copy of a mutated mismatch repair gene is enough to cause disease phenotype. Mutations in the MSH2 gene account for 40% of genetic alterations associated with this disease and is the leading cause, together with MLH1 mutations.^[4] Mutations associated with HNPCC are broadly distributed in all domains of MSH2, and hypothetical functions of these mutations based on the crystal structure of the MutSα include protein-protein interactions, stability, allosteric regulation, MSH2-MSH6 interface, and DNA binding.^[5] Mutations in MSH2 and other mismatch repair genes cause DNA damage to go unrepaired, resulting in an increase in mutation frequency. These mutations build up over a person's life that otherwise would not have occurred had the DNA been repaired properly.

Microsatellite instability

The viability of MMR genes including MSH2 can be tracked via microsatellite instability, a biomarker test that analyzes short sequence repeats which are very difficult for cells to replicate without a functioning mismatch repair system. Because these sequences vary in the population, the actual number of copies of short sequence repeats does not matter, just that the number the patient does have is consistent from tissue to tissue and over time. This phenomena occurs because these sequences are prone to mistakes by the DNA replication complex, which then need to be fixed by the mismatch repair genes. If these are not working, over time either duplications or deletions of these sequences will occur, leading to different numbers of repeats in the same patient.

71% of HNPCC patients show microsatellite instability.^[6] Detection methods for microsatellite instability include polymerase chain reaction (PCR) and immunohistochemical (IHC) methods, polymerase chain checking the DNA and immunohistochemical surveying mismatch repair protein levels. "Currently, there are evidences that universal testing for MSI starting with either IHC or PCR-based MSI testing is cost effective, sensitive, specific and is generally widely accepted."^[7]

Role in mismatch repair

In eukaryotes from yeast to humans, MSH2 dimerizes with MSH6 to form the MutSα complex,^[8] which is involved in base mismatch repair and short insertion/deletion loops.^[9] MSH2 heterodimerization stabilizes MSH6, which is not stable because of its N-terminal disordered domain. Conversely, MSH2 does not have a nuclear localization sequence (NLS), so it is believed that MSH2 and MSH6 dimerize in the cytoplasm and then are imported into the nucleus together.^[10] In the MutSα dimer, MSH6 interacts with the DNA for mismatch recognition while MSH2 provides the stability that MSH6 requires. MSH2 can be imported into the nucleus without dimerizing to MSH6, in this case, MSH2 is probably dimerized to MSH3 to form MutSβ.^[11] MSH2 has two interacting domains with MSH6 in the MutSα heterodimer, a DNA interacting domain, and an ATPase domain.^[12]

The MutSα dimer scans double stranded DNA in the nucleus, looking for mismatched bases. When the complex finds one, it repairs the mutation in an ATP dependent manner. The MSH2 domain of MutSα prefers ADP to ATP, with the MSH6 domain preferring the opposite. Studies have indicated that MutSα only scans DNA with the MSH2 domain harboring ADP, while the MSH6 domain can contain either ADP or ATP.^[13] MutSα then associates with MLH1 to repair the damaged DNA.

MutSβ is formed when MSH2 complexes with MSH3 instead of MSH6. This dimer repairs longer insertion/deletion loops than MutSα.^[14] Because of the nature of the mutations that this complex repairs, this is probably the state of MSH2 that causes the microsatellite instability phenotype. Large DNA insertions and deletions intrinsically bend the DNA double helix. The MSH2/MSH3 dimer can recognize this topology and initiate repair. The mechanism by which it recognizes mutations is different as well, because it separates the two DNA strands, which MutSα does not.^[15]

Interactions

MSH2 has been shown to interact with:

ATR,^[16]^[17]
BRCA1,^[18]
CHEK2,^[19]^[20]
EXO1,^[21]^[22]^[23]
MAX,^[24]
MSH3,^[12]^[16]^[25]^[26]
MSH6,^[12]^[16]^[18]^[25]^[26] and
p53.^[27]

References

^ Mellon I, Rajpal DK, Koi M, Boland CR, Champe GN (April 1996). "Transcription-coupled repair deficiency and mutations in human mismatch repair genes". Science 272 (5261): 557–60. doi:10.1126/science.272.5261.557. PMID 8614807.
^ de Wind N, Dekker M, Berns A, Radman M, te Riele H (July 1995). "Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer". Cell 82 (2): 321–30. doi:10.1016/0092-8674(95)90319-4. PMID 7628020.
^ Pitsikas P, Lee D, Rainbow AJ (May 2007). "Reduced host cell reactivation of oxidative DNA damage in human cells deficient in the mismatch repair gene hMSH2". Mutagenesis 22 (3): 235–43. doi:10.1093/mutage/gem008. PMID 17351251.
^ Müller A, Fishel R (2002). "Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC)". Cancer Invest. 20 (1): 102–9. doi:10.1081/cnv-120000371. PMID 11852992.
^ Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS (May 2007). "Structure of the human MutSalpha DNA lesion recognition complex". Mol. Cell 26 (4): 579–92. doi:10.1016/j.molcel.2007.04.018. PMID 17531815.
^ Bonis PA, Trikalinos TA, Chung M, Chew P, Ip S, DeVine DA, Lau J (May 2007). "Hereditary nonpolyposis colorectal cancer: diagnostic strategies and their implications". Evid Rep Technol Assess (Full Rep) (150): 1–180. PMID 17764220.
^ Zhang X, Li J (February 2013). "Era of universal testing of microsatellite instability in colorectal cancer". World J Gastrointest Oncol 5 (2): 12–9. doi:10.4251/wjgo.v5.i2.12. PMC 3613766. PMID 23556052.
^ Hargreaves VV, Shell SS, Mazur DJ, Hess MT, Kolodner RD (March 2010). "Interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex". J. Biol. Chem. 285 (12): 9301–10. doi:10.1074/jbc.M109.096388. PMC 2838348. PMID 20089866.
^ Drummond JT, Li GM, Longley MJ, Modrich P (June 1995). "Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells". Science 268 (5219): 1909–12. doi:10.1126/science.7604264. PMID 7604264.
^ Christmann M, Kaina B (November 2000). "Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents". J. Biol. Chem. 275 (46): 36256–62. doi:10.1074/jbc.M005377200. PMID 10954713.
^ Edelbrock MA, Kaliyaperumal S, Williams KJ (February 2013). "Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities". Mutat. Res. 743-744: 53–66. doi:10.1016/j.mrfmmm.2012.12.008. PMID 23391514.
^ ^a ^b ^c Guerrette S, Wilson T, Gradia S, Fishel R (November 1998). "Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer". Mol. Cell. Biol. 18 (11): 6616–23. PMC 109246. PMID 9774676.
^ Qiu R, DeRocco VC, Harris C, Sharma A, Hingorani MM, Erie DA, Weninger KR (May 2012). "Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signalling". EMBO J. 31 (11): 2528–40. doi:10.1038/emboj.2012.95. PMID 22505031.
^ Dowen JM, Putnam CD, Kolodner RD (July 2010). "Functional studies and homology modeling of Msh2-Msh3 predict that mispair recognition involves DNA bending and strand separation". Mol. Cell. Biol. 30 (13): 3321–8. doi:10.1128/MCB.01558-09. PMC 2897569. PMID 20421420.
^ Gupta S, Gellert M, Yang W (January 2012). "Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops". Nat. Struct. Mol. Biol. 19 (1): 72–8. doi:10.1038/nsmb.2175. PMC 3252464. PMID 22179786.
^ ^a ^b ^c Wang Y, Qin J (December 2003). "MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation". Proc. Natl. Acad. Sci. U.S.A. 100 (26): 15387–92. doi:10.1073/pnas.2536810100. PMC 307577. PMID 14657349.
^ Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene MI (August 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. PMID 11498787.
^ ^a ^b Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. doi:10.1101/gad.14.8.927. PMC 316544. PMID 10783165.
^ Adamson AW, Beardsley DI, Kim WJ, Gao Y, Baskaran R, Brown KD (March 2005). "Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2". Mol. Biol. Cell 16 (3): 1513–26. doi:10.1091/mbc.E04-02-0089. PMC 551512. PMID 15647386.
^ Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, Baskaran R (January 2003). "The mismatch repair system is required for S-phase checkpoint activation". Nat. Genet. 33 (1): 80–4. doi:10.1038/ng1052. PMID 12447371.
^ Rasmussen LJ, Rasmussen M, Lee B, Rasmussen AK, Wilson DM, Nielsen FC, Bisgaard HC (June 2000). "Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis". Mutat. Res. 460 (1): 41–52. doi:10.1016/S0921-8777(00)00012-4. PMID 10856833.
^ Schmutte C, Marinescu RC, Sadoff MM, Guerrette S, Overhauser J, Fishel R (October 1998). "Human exonuclease I interacts with the mismatch repair protein hMSH2". Cancer Res. 58 (20): 4537–42. PMID 9788596.
^ Schmutte C, Sadoff MM, Shim KS, Acharya S, Fishel R (August 2001). "The interaction of DNA mismatch repair proteins with human exonuclease I". J. Biol. Chem. 276 (35): 33011–8. doi:10.1074/jbc.M102670200. PMID 11427529.
^ Mac Partlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST, Matheson EC, Hall AG, Gillespie DA, Brown R (February 2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene 22 (6): 819–25. doi:10.1038/sj.onc.1206252. PMID 12584560.
^ ^a ^b Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce CM, Copeland T, Kovatich AJ, Fishel R (February 1999). "hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis". Cancer Res. 59 (4): 816–22. PMID 10029069.
^ ^a ^b Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R (November 1996). "hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13629–34. doi:10.1073/pnas.93.24.13629. PMC 19374. PMID 8942985.
^ Scherer SJ, Welter C, Zang KD, Dooley S (April 1996). "Specific in vitro binding of p53 to the promoter region of the human mismatch repair gene hMSH2". Biochem. Biophys. Res. Commun. 221 (3): 722–8. doi:10.1006/bbrc.1996.0663. PMID 8630028.

External links

MutS Homolog 2 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 大腸癌の分子遺伝学 molecular genetics of colorectal cancer
2. リンチ症候群（遺伝性非ポリポーシス大腸癌）の臨床的特徴および診断 clinical features and diagnosis of lynch syndrome hereditary nonpolyposis colorectal cancer
3. ケラトアカントーマ：疫学、危険因子、および診断 keratoacanthoma epidemiology risk factors and diagnosis
4. 大腸癌の病理および予後決定因子 pathology and prognostic determinants of colorectal cancer
5. リンチ症候群（遺伝性非ポリポーシス性大腸癌）の女性における子宮体癌および卵巣癌の
スクリーニングおよび予防 endometrial and ovarian cancer screening and prevention in women with lynch syndrome hereditary nonpolyposis colorectal cancer

English Journal

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer.

Andersson U1, Wibom C1, Cederquist K1, Aradottir S1, Borg A1, Armstrong GN1, Shete S1, Lau CC1, Bainbridge MN1, Claus EB1, Barnholtz-Sloan J1, Lai R1, Il'yasova D1, Houlston RS1, Schildkraut J1, Bernstein JL1, Olson SH1, Jenkins RB1, Lachance DH1, Wrensch M1, Davis FG1, Merrell R1, Johansen C1, Sadetzki S1; Gliogene Consortium, Bondy ML1, Melin BS1; Gliogene Consortium.
Neuro-oncology.Neuro Oncol.2014 Oct;16(10):1333-40. doi: 10.1093/neuonc/nou052. Epub 2014 Apr 9.
BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer
PMID 24723567

Can a cancer cell turn into a normal cell?

Aktaş RG.
JOP : Journal of the pancreas.JOP.2014 Sep 28;15(5):2789. doi: 10.6092/1590-8577/2789.
HepG2 cells, a human liver cancer cell line (hepatocellular carcinoma), are being considered as a future model for bioartificial liver studies. They have the ability to differentiate and demonstrate some features of normal liver cells. Our previous studies focused on examination of the morphological
PMID 25262743

Japanese Journal

1) ゲノム不安定性・遺伝子変異に基づく子宮体癌の浸潤能獲得と分子生物学的予後不良因子の検討(シンポジウム1:腫瘍「婦人科癌の浸潤・転移機構の解明と臨床応用」,第65回日本産科婦人科学会・学術講演会講演要旨)

織田克利
日本産科婦人科學會雜誌 65(10), 2388-2401, 2013-10-01
… MSI is caused by deficiency of DNA mismatch repair genes (MMR), including MLH1 and MSH2, and is associated with mutator phenotype. …
NAID 110009674401

Genomic stability in Nicotiana plants upon silencing of the mismatch repair gene MSH2

Van Marcke Inke,Angenon Geert
Plant biotechnology reports 7(4), 467-480, 2013-10
NAID 40019926576

Lynch症候群に発症し急速に進行したIIc類似進行大腸癌の1例

後藤規弘,山口大介,田中泰敬,臼井智彦,中井喜貴,藤井茂彦,畦地英全,日下利広,國立裕之,安原裕美子
日本消化器内視鏡学会雑誌 55(12), 3770-3775, 2013
… 横行結腸癌（59歳）の手術施行後であった．大腸癌術後に1年毎に施行されていた下部消化管内視鏡検査にて上行結腸に15mm大の平坦陥凹病変を認め，IIc類似進行大腸癌と診断し右半結腸切除術を施行した（Stage IIIb，pT3N2M0）．ミスマッチ修復遺伝子検査では<I>MSH2</I>の変異を認めLynch症候群と診断された．Lynch症候群では，本症例のように急速な進行をきたす病変を念頭に置いてサーベイランスを行う必要がある． …
NAID 130003386607

Related Pictures

Solar Spektre Modelo Memento Msh2 -354 Начало Synthetic Handball Ball MSH2 model depicting Msh2-Msh6 movement on DNA Protein MSH2 PDB 2o8b.png Heater / Mistral Instant Water Heater MSH2 Opiniones de MSH2 Msh2-Msh3 Interferes with Okazaki Fragment Yamaha MSH2 Marching Stick Bag - Double

★リンクテーブル★

リンク元	「癌」
関連記事	「MS」「MSH」

「癌」

MutS homolog 2
	PDB rendering based on 2o8b.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2O8B, 2O8C, 2O8D, 2O8E, 2O8F, 3THW, 3THX, 3THY, 3THZ
Identifiers
Symbols	MSH2 ; COCA1; FCC1; HNPCC; HNPCC1; LCFS2
External IDs	OMIM: 609309 MGI: 101816 HomoloGene: 210 GeneCards: MSH2 Gene
Gene ontology
Molecular function	• magnesium ion binding; • four-way junction DNA binding; • Y-form DNA binding; • heteroduplex DNA loop binding; • double-strand/single-strand DNA junction binding; • DNA binding; • double-stranded DNA binding; • single-stranded DNA binding; • protein binding; • ATP binding; • protein C-terminus binding; • DNA-dependent ATPase activity; • ATPase activity; • centromeric DNA binding; • enzyme binding; • protein kinase binding; • mismatched DNA binding; • guanine/thymine mispair binding; • dinucleotide insertion or deletion binding; • single guanine insertion binding; • single thymine insertion binding; • dinucleotide repeat insertion binding; • oxidized purine DNA binding; • MutLalpha complex binding; • protein homodimerization activity; • ADP binding;
Cellular component	• nuclear chromosome; • nucleoplasm; • membrane; • MutSalpha complex; • MutSbeta complex;
Biological process	• meiotic mismatch repair; • in utero embryonic development; • oxidative phosphorylation; • DNA repair; • mismatch repair; • postreplication repair; • double-strand break repair; • meiotic gene conversion; • cell cycle arrest; • reciprocal meiotic recombination; • germ cell development; • determination of adult lifespan; • male gonad development; • response to X-ray; • response to UV-B; • somatic hypermutation of immunoglobulin genes; • somatic recombination of immunoglobulin gene segments; • B cell mediated immunity; • B cell differentiation; • intra-S DNA damage checkpoint; • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; • negative regulation of neuron apoptotic process; • maintenance of DNA repeat elements; • negative regulation of reciprocal meiotic recombination; • isotype switching; • negative regulation of DNA recombination; • positive regulation of helicase activity;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: cancer
関: 悪性腫瘍

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

http://ganjoho.ncc.go.jp/public/statistics/pub/statistics01.html

●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
autoimmune lymphoproliferative syndrome	FASL	1q23		lymphomas
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
hereditary breast/ovarian cancer	BRCA2	13q12.3		breast, ovarian, colon, prostate
hereditary diffuse gastric cancer	CDH1	16q22	AD	stomach cancers
hereditary multiple exostoses	EXT1	8q24	AD	exostoses, chondrosarcoma
hereditary multiple exostoses	EXT2	11p11-12		exostoses, chondrosarcoma
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
tuberous sclerosis	TSC2	16p13.3		angiofibroma, renal angiomyolipoma
von Hippel–Lindau	VHL	3p25-26	AD	kidney, cerebellum, pheochromocytoma

癌遺伝子、癌抑制遺伝子

癌の危険因子

生活習慣病#生活習慣病などのリスクファクターを改変

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

「MS」

　　[★]

「MSH」

　　[★] メラニン細胞刺激ホルモン melanocyte-stimulating hormone

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[pmid17351251-3] Pitsikas P, Lee D, Rainbow AJ (May 2007). "Reduced host cell reactivation of oxidative DNA damage in human cells deficient in the mismatch repair gene hMSH2". Mutagenesis 22 (3): 235–43. doi:10.1093/mutage/gem008. PMID 17351251.

[pmid11852992-4] Müller A, Fishel R (2002). "Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC)". Cancer Invest. 20 (1): 102–9. doi:10.1081/cnv-120000371. PMID 11852992.

[pmid17531815-5] Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS (May 2007). "Structure of the human MutSalpha DNA lesion recognition complex". Mol. Cell 26 (4): 579–92. doi:10.1016/j.molcel.2007.04.018. PMID 17531815.

[pmid17764220-6] Bonis PA, Trikalinos TA, Chung M, Chew P, Ip S, DeVine DA, Lau J (May 2007). "Hereditary nonpolyposis colorectal cancer: diagnostic strategies and their implications". Evid Rep Technol Assess (Full Rep) (150): 1–180. PMID 17764220.

[pmid23556052-7] Zhang X, Li J (February 2013). "Era of universal testing of microsatellite instability in colorectal cancer". World J Gastrointest Oncol 5 (2): 12–9. doi:10.4251/wjgo.v5.i2.12. PMC 3613766. PMID 23556052.

[pmid20089866-8] Hargreaves VV, Shell SS, Mazur DJ, Hess MT, Kolodner RD (March 2010). "Interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex". J. Biol. Chem. 285 (12): 9301–10. doi:10.1074/jbc.M109.096388. PMC 2838348. PMID 20089866.

[pmid7604264-9] Drummond JT, Li GM, Longley MJ, Modrich P (June 1995). "Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells". Science 268 (5219): 1909–12. doi:10.1126/science.7604264. PMID 7604264.

[pmid10954713-10] Christmann M, Kaina B (November 2000). "Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents". J. Biol. Chem. 275 (46): 36256–62. doi:10.1074/jbc.M005377200. PMID 10954713.

[pmid23391514-11] Edelbrock MA, Kaliyaperumal S, Williams KJ (February 2013). "Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities". Mutat. Res. 743-744: 53–66. doi:10.1016/j.mrfmmm.2012.12.008. PMID 23391514.

[pmid9774676-12] Guerrette S, Wilson T, Gradia S, Fishel R (November 1998). "Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer". Mol. Cell. Biol. 18 (11): 6616–23. PMC 109246. PMID 9774676.

[pmid22505031-13] Qiu R, DeRocco VC, Harris C, Sharma A, Hingorani MM, Erie DA, Weninger KR (May 2012). "Large conformational changes in MutS during DNA scanning, mismatch recognition and repair signalling". EMBO J. 31 (11): 2528–40. doi:10.1038/emboj.2012.95. PMID 22505031.

[pmid20421420-14] Dowen JM, Putnam CD, Kolodner RD (July 2010). "Functional studies and homology modeling of Msh2-Msh3 predict that mispair recognition involves DNA bending and strand separation". Mol. Cell. Biol. 30 (13): 3321–8. doi:10.1128/MCB.01558-09. PMC 2897569. PMID 20421420.

[pmid22179786-15] Gupta S, Gellert M, Yang W (January 2012). "Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops". Nat. Struct. Mol. Biol. 19 (1): 72–8. doi:10.1038/nsmb.2175. PMC 3252464. PMID 22179786.

[pmid14657349-16] Wang Y, Qin J (December 2003). "MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation". Proc. Natl. Acad. Sci. U.S.A. 100 (26): 15387–92. doi:10.1073/pnas.2536810100. PMC 307577. PMID 14657349.

[pmid11498787-17] Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene MI (August 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. PMID 11498787.

[pmid10783165-18] Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. doi:10.1101/gad.14.8.927. PMC 316544. PMID 10783165.

[pmid15647386-19] Adamson AW, Beardsley DI, Kim WJ, Gao Y, Baskaran R, Brown KD (March 2005). "Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2". Mol. Biol. Cell 16 (3): 1513–26. doi:10.1091/mbc.E04-02-0089. PMC 551512. PMID 15647386.

[pmid12447371-20] Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, Baskaran R (January 2003). "The mismatch repair system is required for S-phase checkpoint activation". Nat. Genet. 33 (1): 80–4. doi:10.1038/ng1052. PMID 12447371.

[pmid10856833-21] Rasmussen LJ, Rasmussen M, Lee B, Rasmussen AK, Wilson DM, Nielsen FC, Bisgaard HC (June 2000). "Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis". Mutat. Res. 460 (1): 41–52. doi:10.1016/S0921-8777(00)00012-4. PMID 10856833.

[pmid9788596-22] Schmutte C, Marinescu RC, Sadoff MM, Guerrette S, Overhauser J, Fishel R (October 1998). "Human exonuclease I interacts with the mismatch repair protein hMSH2". Cancer Res. 58 (20): 4537–42. PMID 9788596.

[pmid11427529-23] Schmutte C, Sadoff MM, Shim KS, Acharya S, Fishel R (August 2001). "The interaction of DNA mismatch repair proteins with human exonuclease I". J. Biol. Chem. 276 (35): 33011–8. doi:10.1074/jbc.M102670200. PMID 11427529.

[pmid12584560-24] Mac Partlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST, Matheson EC, Hall AG, Gillespie DA, Brown R (February 2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene 22 (6): 819–25. doi:10.1038/sj.onc.1206252. PMID 12584560.

[pmid10029069-25] Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce CM, Copeland T, Kovatich AJ, Fishel R (February 1999). "hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis". Cancer Res. 59 (4): 816–22. PMID 10029069.

[pmid8942985-26] Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R (November 1996). "hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13629–34. doi:10.1073/pnas.93.24.13629. PMC 19374. PMID 8942985.

[pmid8630028-27] Scherer SJ, Welter C, Zang KD, Dooley S (April 1996). "Specific in vitro binding of p53 to the promoter region of the human mismatch repair gene hMSH2". Biochem. Biophys. Res. Commun. 221 (3): 722–8. doi:10.1006/bbrc.1996.0663. PMID 8630028.

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MSH2