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• W2107337152 abstract "We set out to determine whether hereditary nonpolyposis colorectal cancer (HNPCC) was responsible for cancer susceptibility in a family with gynecologic malignancies in three consecutive generations.A detailed family history study, including review of medical records, was undertaken. Tumor DNAs from affected family members were evaluated for microsatellite instability (MSI). Linkage between cancer susceptibility and the candidate DNA mismatch repair genes MLH1, MSH2, MSH3, and MSH6 (GTBP) was investigated. MLH1 and MSH2 protein expression was evaluated by immunohistochemistry and MSH2 was investigated for mutation.Four gynecologic malignancies in the core family were confirmed. MSI was seen in six of seven cancers studied. The only MSI-negative tumor was an ovarian cancer from the proband's maternal grandmother, which arose at the age of 92. Haplotype analysis using chromosome 2p markers implicated the MSH2 gene in this family's cancer susceptibility. MSH2 protein expression was absent in an MSI-positive colon cancer from an affected family member.The inability to exclude linkage of MSH2 with the disease susceptibility, the presence of the MSI phenotype in cancers from family members sharing the same region of chromosome 2p, and the lack of immunodetectable MSH2 point to MSH2-associated HNPCC as a cause for this family's cancer susceptibility. Continued efforts to increase awareness of the heritability of endometrial cancer should improve our understanding of the disease, with resultant improved surveillance strategies, recommendations for surgical and chemoprophylaxis, and identification of patients at risk for malignancy as a result of HNPCC." @default.
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• W2107337152 date "2000-04-01" @default.
• W2107337152 modified "2023-09-25" @default.
• W2107337152 title "Atypical Clustering of Gynecologic Malignancies: A Family Study Including Molecular Analysis of Candidate Genes" @default.
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• W2107337152 doi "https://doi.org/10.1006/gyno.1999.5709" @default.
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