Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer

Karin Kast,Wolfgang Distler,Heike Görgens,Kerstin Becker,Katja Keller,Hans K Schackert,Barbara Klink,Evelin Schröck,Teresa M Neuhann,Daniela Aust

doi:10.1186/1471-2407-12-531

Karin Kast, Wolfgang Distler + Show 8 more

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https://doi.org/10.1186/1471-2407-12-531

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BackgroundHereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare.Case presentationWe identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years.ConclusionsAlthough carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.

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Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers
Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) is an autosomal dominantly inherited disease caused by mutations in BRCA1 or BRCA2 and characterized by young age of onset, synchronous or metachronous disease, and a family history of first and second degree relatives with breast and/or ovarian cancer
Lynch syndrome, is an autosomal dominant tumor predisposition caused by germline mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 with a life-time risk for colorectal cancer (CRC) of up to 80% and considerably increased risk of developing a broad spectrum of extracolonic malignancies including, among others, endometrial cancer (EC), stomach cancer and ovarian cancer [3,4]

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Conclusions

Only two families with co-occurrence of a MMR and BRCA1/BRCA2 mutation have been reported [16,17]. Carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations, anamnestical and histopathological findings may guide clinicians to identify these families Meeting both Bethesda Guidelines and HBOCS Criteria may raise suspicion of both syndromes in one family. This may be substantiated by specific histological findings in available tumors, such as triple negative breast cancers (BRCA1associated), high grade papillary serous ovarian cancer (BRCA1- and 2-associated), endometrioid cancer of the uterus (MMR-gene-associated) and microsatellite instability (MMR-gene-associated). Both syndromes can only be diagnosed through a complete gene analysis of the respective genes.

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