Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer - PubMed (original) (raw)
. 2006 Oct;38(10):1178-83.
doi: 10.1038/ng1866. Epub 2006 Sep 3.
Affiliations
- PMID: 16951683
- DOI: 10.1038/ng1866
Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer
Tsun Leung Chan et al. Nat Genet. 2006 Oct.
Abstract
Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.
Comment in
- Heritable germline epimutations in humans.
Horsthemke B. Horsthemke B. Nat Genet. 2007 May;39(5):573-4; author reply 575-6. doi: 10.1038/ng0507-573b. Nat Genet. 2007. PMID: 17460680 No abstract available. - Inherited epimutation or a haplotypic basis for the propensity to silence?
Suter CM, Martin DI. Suter CM, et al. Nat Genet. 2007 May;39(5):573; author reply 576. doi: 10.1038/ng0507-573a. Nat Genet. 2007. PMID: 17460681 No abstract available. - Heritable germline epimutation is not the same as transgenerational epigenetic inheritance.
Chong S, Youngson NA, Whitelaw E. Chong S, et al. Nat Genet. 2007 May;39(5):574-5; author reply 575-6. doi: 10.1038/ng0507-574. Nat Genet. 2007. PMID: 17460682 No abstract available.
Similar articles
- Multiple epithelial and nonepithelial tumors in hereditary nonpolyposis colorectal cancer: characterization of germline and somatic mutations of the MSH2 gene and heterogeneity of replication error phenotypes.
Huang RL, Chao CF, Ding DC, Yu CP, Chang CC, Lai HC, Yu MH, Liu HS, Chu TY. Huang RL, et al. Cancer Genet Cytogenet. 2004 Sep;153(2):108-14. doi: 10.1016/j.cancergencyto.2004.01.003. Cancer Genet Cytogenet. 2004. PMID: 15350299 - A novel missense MSH2 gene mutation in a patient of a Korean family with hereditary nonpolyposis colorectal cancer.
Park SJ, Lee KA, Park TS, Kim NK, Song J, Kim BY, Choi JR. Park SJ, et al. Cancer Genet Cytogenet. 2008 Apr 15;182(2):136-9. doi: 10.1016/j.cancergencyto.2008.01.011. Cancer Genet Cytogenet. 2008. PMID: 18406877 - Medullary carcinoma of the pancreas in a man with hereditary nonpolyposis colorectal cancer due to a mutation of the MSH2 mismatch repair gene.
Banville N, Geraghty R, Fox E, Leahy DT, Green A, Keegan D, Geoghegan J, O'Donoghue D, Hyland J, Sheahan K. Banville N, et al. Hum Pathol. 2006 Nov;37(11):1498-502. doi: 10.1016/j.humpath.2006.06.024. Epub 2006 Sep 25. Hum Pathol. 2006. PMID: 16996571 - Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation.
Hitchins MP. Hitchins MP. Fam Cancer. 2016 Jul;15(3):413-22. doi: 10.1007/s10689-016-9887-3. Fam Cancer. 2016. PMID: 26886015 Review. - [Germ-line epimutations and human cancer].
Wu PY, Fan YM, Wang YP. Wu PY, et al. Ai Zheng. 2009 Dec;28(12):1236-42. doi: 10.5732/cjc.009.10266. Ai Zheng. 2009. PMID: 19958615 Review. Chinese.
Cited by
- Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease.
Li Y, Bai H, Liu W, Zhou W, Gu H, Zhao P, Zhu M, Li Y, Yan X, Zhao N, Huang X. Li Y, et al. iScience. 2024 Jul 25;27(8):110588. doi: 10.1016/j.isci.2024.110588. eCollection 2024 Aug 16. iScience. 2024. PMID: 39220410 Free PMC article. - Methylation marks in blood DNA reveal breast cancer risk in patients fulfilling hereditary disease criteria.
Ruiz-De La Cruz M, Martínez-Gregorio H, Estela Díaz-Velásquez C, Ambriz-Barrera F, Resendiz-Flores NG, Gitler-Weingarten R, Rojo-Castillo MP, Pradda D, Oliver J, Perdomo S, Gómez-García EM, De La Cruz-Montoya AH, Terrazas LI, Torres-Mejía G, Hernández-Hernández FC, Vaca-Paniagua F. Ruiz-De La Cruz M, et al. NPJ Precis Oncol. 2024 Jun 19;8(1):136. doi: 10.1038/s41698-024-00611-z. NPJ Precis Oncol. 2024. PMID: 38898118 Free PMC article. - Unraveling noncoding DNA variants and epimutations: a paradigm shift in hereditary cancer research.
Ibrahim MB, Flanagan J, Ibrahim T, Rouleau E. Ibrahim MB, et al. Future Oncol. 2024;20(18):1289-1298. doi: 10.2217/fon-2023-0665. Epub 2024 May 9. Future Oncol. 2024. PMID: 38722139 Review. - Lynch Syndrome: From Multidisciplinary Management to Precision Prevention.
Dal Buono A, Puccini A, Franchellucci G, Airoldi M, Bartolini M, Bianchi P, Santoro A, Repici A, Hassan C. Dal Buono A, et al. Cancers (Basel). 2024 Feb 20;16(5):849. doi: 10.3390/cancers16050849. Cancers (Basel). 2024. PMID: 38473212 Free PMC article. Review. - Lynch-like Syndrome: Potential Mechanisms and Management.
Martínez-Roca A, Giner-Calabuig M, Murcia O, Castillejo A, Soto JL, García-Heredia A, Jover R. Martínez-Roca A, et al. Cancers (Basel). 2022 Feb 22;14(5):1115. doi: 10.3390/cancers14051115. Cancers (Basel). 2022. PMID: 35267422 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources