BRCA1 and BRCA2 mutations in ovarian cancer patients from Belarus: update

Abstract

Background Mutations in BRCA1 and BRCA2 are well-established risk factors for breast and ovarian cancer. In Central-Eastern European counties, the founder mutations in the BRCA1 are responsible for a significant proportion of ovarian cancer cases, however, regional differences in the frequencies of various mutations may exist. The spectrum and frequency of BRCA1/2 mutations between ovarian cancer patients have not yet been precisely established in Belarus. Methods Two hundred fourteen consecutive unselected cases of ovarian cancer patients from the region of West Belarus were examined. We studied 13 founder mutations in BRCA1 (c.5266dupC, c.4035delA, c.5251C > T, c.181 T > G, c.676delT, c.68_69delAG, c.3700_3704delGTAAA, c.1687C > T, c.3756_3759delGTCT) and in BRCA2 (c.658_659delGT, c.7913_7917delTTCCT, c.3847_3848delGT, c.5946delT) characteristic for Central European population. Results A BRCA1 or BRCA2 founder mutations were detected in 54 of the 214 (25.2%) ovarian cancer cases. The BRCA1 c.5266dupC mutation was detected in 28 patients, followed by c.4035delA mutation observed in 18 patients. BRCA1 c.3756_3759delGTCT, c.68_69delAG, and c.1687C > T were found in 3, 2, and 1 women, respectively. BRCA2 c.658_659delGT mutation was detected in 2 ovarian cancer patients. The median age of diagnosis of the 54 hereditary ovarian cancers was 57.5 years. Conclusions The frequency of 13 causative BRCA1 and BRCA2 founder mutations in West Belarus was higher than in other Slavic countries. Testing of BRCA1 (c.5266dupC, c.4035delA, c.3756_3759delGTCT, c.68_69delAG, c.1687C > T as well as c.181 T > G) and BRCA2 (c.658_659delGT) mutations should be considered an inexpensive and sensitive test panel for this population.

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients

“…This variant is not seen in other populations. Another common mutation BRCA1 c.3756_3759delGTCT has been detected in some populations, such as Thai [55], Polish [56], Belarusian [57], Italian [58], French-Canadian [59], and Czech populations [60]. BRCA1 c.4065_4068del has been detected in some populations [61][62][63].…”

A case of ovarian carcinosarcoma with a germline pathogenic variant of BRCA2 involving a perforated appendix with an abscess

“…11 The BRCA2 c.658_659delGT; p.Val220fs variant (rs80359604), also known as 886delGT, is reported in several women with hereditary breast and ovarian cancer syndrome. 12,13 GPVs of BRCA1/BRCA2 are predicted to be found in patients with ovarian cancer who are sensitive to platinum-based antineoplastic medicines. These patients also have a better prognosis than those without a GPV of BRCA1/BRCA2.…”

“…1,2 Molecular studies have suggested that OCS tumors might have epithelial cell origins, and the sarcomatous components may be derived from the carcinomatous components, since both components share common genetic alterations and are monoclonal. 8,13 Most of the data addressing the genetic origin of carcinosarcomas in gynecologic tumors is from studies of uterine carcinosarcoma specimens. 2 The carcinomatous component of OCS dictates tumor behaviour, 1,2 although OCS is associated with a poor prognosis compared with high-grade serous carcinoma.…”

Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer

“…Given that only a subset of these patients belongs to clinical subgroups with hereditary features of cancer predisposition (e.g., early‐onset, family history, or disease bilaterality for BC patients, or high‐grade serous histology for OC patients), we estimated that it may take years to collect a substantial number of these patients prospectively. Several reports demonstrated that consecutive (i.e., unselected for family history or age at onset) series of high‐grade serous OC (HGSOC) were characterized by a high frequency of BRCA1/2 mutations 8–10 . We anticipated that the retrospective analysis of relatively small numbers of HGSOC patients would reveal whether BRCA1/2 germline mutations persist in the Chechen population and whether the detection of BRCA1/2 pathogenic variants can be simplified because of the existence of a founder effect.…”

“…Several reports demonstrated that consecutive (i.e., unselected for family history or age at onset) series of high‐grade serous OC (HGSOC) were characterized by a high frequency of BRCA1/2 mutations. 8 , 9 , 10 We anticipated that the retrospective analysis of relatively small numbers of HGSOC patients would reveal whether BRCA1/2 germline mutations persist in the Chechen population and whether the detection of BRCA1/2 pathogenic variants can be simplified because of the existence of a founder effect.…”