BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. Issue 2 (18th July 2012)

• Record Type: Journal Article
• Authors: Pennington, Kathryn P.; Walsh, Tom; Lee, Ming; Pennil, Christopher; Novetsky, Akiva P.; Agnew, Kathy J.; Thornton, Anne; Garcia, Rochelle; Mutch, David; King, Mary‐Claire; Goodfellow, Paul; Swisher, Elizabeth M.
• Is Part Of: Cancer. Volume 119:Issue 2(2013)
• Page Start: 332
• Page End: 338
• Publication Date: 2012-07-18
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.27720
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>BACKGROUND:</title> <p>Uterine serous carcinoma (USC) is not recognized as part of any defined hereditary cancer syndrome, and its association with hereditary breast and ovarian carcinoma and Lynch syndrome are uncertain.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>METHODS:</title> <p>Using targeted capture and massively parallel genomic sequencing, 151 subjects with USC were assessed for germline mutations in 30 tumor suppressor genes, including <italic>BRCA1</italic> (breast cancer 1, early onset), <italic>BRCA2</italic>, the DNA mismatch repair genes (<italic>MLH1</italic> [mutL homolog 1], <italic>MSH2</italic> [mutS homolog 2], <italic>MSH6</italic>, <italic>PMS2</italic> [postmeiotic segregation increased 2]), <italic>TP53</italic> (tumor protein p53), and 10 other genes in the Fanconi anemia–BRCA pathway. Ten cases with < 10% serous histology were also assessed.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>RESULTS:</title> <p>Seven subjects (4.6%) carried germline loss‐of‐function mutations: 3 subjects (2.0%) with mutations in <italic>BRCA1</italic>, 2 subjects (1.3%) with mutations in <italic>TP53</italic>, and 2 subjects (1.3%) with mutations in <italic>CHEK2</italic> (checkpoint kinase 2). One subject with < 10% serous histology had an <italic>MSH6</italic> mutation. Subjects with <italic>MSH6</italic> and <italic>TP53</italic> mutations had neither personal nor family histories suggestive of Lynch or Li‐Fraumeni syndromes. Of the 22 women with USC and a personal history of breast carcinoma, the frequency of <italic>BRCA1</italic> mutations was 9%, compared to 0.9% in 119 women with no such history.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>CONCLUSIONS:</title> <p>Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes<italic>: BRCA1</italic>, <italic>CHEK2</italic>, and <italic>TP53</italic>. Mutations in DNA mismatch repair genes that cause Lynch syndrome are rare in USC. The germline <italic>BRCA1</italic> mutation rate in USC subjects of 2% is higher than expected in a nonfounder population, suggesting that USC is associated with hereditary breast and ovarian carcinoma in a small proportion of cases. Women with USC and breast cancer should be offered genetic testing for <italic>BRCA1</italic> and <italic>BRCA2</italic> mutations. Cancer 2013. © 2012 American Cancer Society.</p> </sec> </abstract>