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Double heterozygosity for BRCA1 and hMLH1 gene mutations in a 46-year-old woman with five primary tumors
Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast cancer, whereas carriers of mutations in any of the mismatch repair genes (MMR; hMLH1 , hMSH2 , hMSH6 , hPMS2 ) are highly susceptible to Lynch syndrome. In the present study, we describe a woman affected by unilateral breas...
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Published in: | Techniques in coloproctology 2014-03, Vol.18 (3), p.285-289 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Germline mutations in
BRCA1
and
BRCA2
genes predispose to hereditary breast cancer, whereas carriers of mutations in any of the mismatch repair genes (MMR;
hMLH1
,
hMSH2
,
hMSH6
,
hPMS2
) are highly susceptible to Lynch syndrome. In the present study, we describe a woman affected by unilateral breast cancer at the age of 35 years. After 4 years, during the follow-up she developed synchronous (and asymptomatic) endometrial cancer, ovarian carcinoma and renal clear cell carcinoma. After 7 years (at age 46), the patient developed an infiltrating carcinoma of the contralateral breast and died in a few months of metastatic disease. Initial investigations led to the detection of a constitutional mutation in the
BRCA1
gene. The extended genealogical tree disclosed a suspected history of colorectal carcinoma in the maternal branch. Endometrial cancer of the proband was investigated for microsatellite instability (MSI) and immunohistochemical expression of MLH1, MSH2 and MSH6 proteins. An high MSI status and lack of expression of MLH1 protein were detected.
hMLH1
gene sequencing revealed the presence of a constitutional mutation, which was also found in the mother of the proband. Loss of the wild-type
hMLH1
allele was detected in both breast tumors, thus suggesting that the MMR defect contributed to the development of the breast cancer. |
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ISSN: | 1123-6337 1128-045X |
DOI: | 10.1007/s10151-013-1030-y |