Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research Demokritos, Athens, Greece.
PLoS One. 2013;8(3):e58182. doi: 10.1371/journal.pone.0058182. Epub 2013 Mar 11.
Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.
BRCA1 和 BRCA2 基因的种系突变导致约 18%的遗传性卵巢癌，估计终生风险为 15%至 50%。不同人群的卵巢癌病例中，这些基因的突变发生率不同。在希腊，BRCA1 中的 6 个突变占 BRCA1 和 BRCA2 基因中检测到的所有突变的 63%。本研究旨在确定 106 例具有强烈家族史或同时患有乳腺癌的希腊家族性卵巢癌患者和 592 例散发性卵巢癌患者中 BRCA1 突变的流行率。对所有 698 例患者进行了 6 种常见希腊突变（包括 c.5266dupC、p.G1738R 以及外显子 20、外显子 23-24 和外显子 24 的三个大片段缺失）的筛查。在家族性病例中，BRCA1 基因随后进行了外显子 5、11、12、20、21、22、23、24 的筛查。在 106 例家族性癌症病例中发现了 43 个（40.6%）有害的 BRCA1 突变，在 592 例散发性病例中发现了 27 个（4.6%）。在 698 例患者中发现了 9 例（1.3%）具有未知临床意义的变体 p.V1833M。大多数 BRCA1 携带者（71.2%）表现为高级别浆液性表型。在乳腺癌和/或卵巢癌家族中鉴定出 BRCA1 基因的突变非常重要，因为它使携带者能够采取预防措施。所有表现为浆液性表型的卵巢癌患者都应考虑进行基因检测。有必要进一步研究确定 BRCA1 基因其余部分、BRCA2 基因以及其他乳腺癌和卵巢癌易感基因的突变流行率。
