MSH6 germline mutations are rare in colorectal cancer families Journal Article
| Authors: | Peterlongo, P.; Nafa, K.; Lerman, G. S.; Glogowski, E.; Shia, J.; Ye, T. Z.; Markowitz, A. J.; Guillem, J. G.; Kolachana, P.; Boyd, J. A.; Offit, K.; Ellis, N. A. |
| Article Title: | MSH6 germline mutations are rare in colorectal cancer families |
| Abstract: | Germline mutations in MSH6 can cause HNPCC, which is associated with a tumor phenotype featuring MSI. However, tumors arising in persons with disease-causing mutations of MSH6 may or may not exhibit MSI. We used D-HPLC to screen for germline mutations in the promoter region, the coding region and the 3′-UTR of MSH6. Eighty-four families, enrolled on the basis of Amsterdam I and II criteria (HNPCC families) and less stringent criteria (HNPCC-like families), were tested for MMR gene mutations; 27 families had a disease-causing mutation in MLHI or MSH2, and the remaining 57 families were tested for mutations in MSH6. Two protein-truncating mutations were identified in each of 2 families fulfilling the Amsterdam I criteria, being present in persons affected with early-onset colorectal cancers exhibiting MSI. Immunohistochemical analysis showed that expression of both MSH2 and MSH6 proteins was lost in the cancer cells of the 2 mutation carriers but only MSH6 protein expression was lost in 2 adenomatous polyps. A third possibly disease-causing mutation was found in a person affected with a tumor that did not exhibit MSI. In addition, we found 4 new polymorphisms and determined that neither of the 2 studied by association analysis conferred susceptibility to colorectal or endometrial cancer. Altogether, our results indicate that disease-causing germline mutations of MSH6 are rare in HNPCC and HNPCC-like families. © 2003 Wiley-Liss, Inc. |
| Keywords: | immunohistochemistry; adult; human tissue; aged; middle aged; gene mutation; major clinical study; promoter region; dna-binding proteins; exons; proto-oncogene proteins; endometrial neoplasms; endometrium cancer; polymerase chain reaction; colorectal cancer; dna repair; cancer susceptibility; heterozygote; pedigree; immunoenzyme techniques; germ line; microsatellite instability; genetic susceptibility; 3' untranslated region; high performance liquid chromatography; chromatography, high pressure liquid; dna mutational analysis; dna primers; genetic screening; onset age; protein msh6; colorectal neoplasms, hereditary nonpolyposis; muts homolog 2 protein; germ-line mutation; linkage (genetics); family; adenomatous polyp; genetic polymorphism; hereditary nonpolyposis colorectal cancer; mismatch repair gene; humans; human; male; female; priority journal; article; denaturation |
| Journal Title: | International Journal of Cancer |
| Volume: | 107 |
| Issue: | 4 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2003-11-20 |
| Start Page: | 571 |
| End Page: | 579 |
| Language: | English |
| DOI: | 10.1002/ijc.11415 |
| PUBMED: | 14520694 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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