Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint-Petersburg, Russia.
Department of Medical Genetics, St.-Petersburg Pediatric Medical University, Saint-Petersburg, Russia.
Breast Cancer Res Treat. 2020 Nov;184(1):229-235. doi: 10.1007/s10549-020-05827-8. Epub 2020 Aug 9.
The spectrum of BRCA1 and BRCA2 mutations in Slavic countries is characterized by a high prevalence of founder alleles.
We analyzed a large data set of Russian breast cancer (BC) and ovarian cancer (OC) patients, who were subjected to founder mutation tests or full-length BRCA1 and BRCA2 analysis.
The most commonly applied test, which included four founder mutations (BRCA1: 5382insC, 4153delA, 185delAG; BRCA2: 6174delT), identified BRCA1 or BRCA2 heterozygosity in 399/8533 (4.7%) consecutive BC patients, 230/2317 (9.9%) OC patients, and 30/118 (25.4%) women with a combination of BC and OC. The addition of another four recurrent BRCA1 mutations to the test (BRCA1 C61G, 2080delA, 3819del5, 3875del4) resulted in evident increase in the number of identified mutation carriers (BC: 16/993 (1.6%); OC: 34/1289 (2.6%); BC + OC: 2/39 (5.1%)). Full-length sequencing of the entire BRCA1 and BRCA2 coding region was applied to 785 women, very most of whom demonstrated clinical signs of BRCA-driven disease, but turned out negative for all described above founder alleles. This analysis revealed additional BRCA1 or BRCA2 mutation carriers in 54/282 (19.1%) BC, 50/472 (10.6%) OC, and 13/31 (42%) BC + OC patients. The analysis of frequencies of founder and "rare" BRCA1 and BRCA2 pathogenic alleles across various clinical subgroups (BC vs. OC vs. BC + OC; family history positive vs. negative; young vs. late-onset; none vs. single vs. multiple clinical indicators of BRCA1- or BRCA2-associated disease) revealed that comprehensive BRCA1 and BRCA2 analysis increased more than twice the number of identified mutation carriers in all categories of the examined women.
Full-length BRCA1 and BRCA2 sequencing is strongly advised to Slavic subjects, who have medical indications for BRCA1 and BRCA2 testing but are negative for recurrent BRCA1 and BRCA2 mutations.
BRCA1 和 BRCA2 突变在斯拉夫国家的频谱特征是高频的创始突变等位基因。
我们分析了大量俄罗斯乳腺癌（BC）和卵巢癌（OC）患者的数据，这些患者接受了创始突变检测或全长 BRCA1 和 BRCA2 分析。
最常用的检测方法包括四个创始突变（BRCA1：5382insC、4153delA、185delAG；BRCA2：6174delT），在 8533 例连续 BC 患者中的 399 例（4.7%）、2317 例 OC 患者中的 230 例（9.9%）和 118 例同时患有 BC 和 OC 的患者中，确定了 BRCA1 或 BRCA2 杂合性。将另外四个常见的 BRCA1 突变（BRCA1 C61G、2080delA、3819del5、3875del4）添加到检测中，明显增加了鉴定的突变携带者数量（BC：16/993（1.6%）；OC：34/1289（2.6%）；BC+OC：2/39（5.1%））。对 785 名女性进行了整个 BRCA1 和 BRCA2 编码区的全长测序，她们中的大多数都有 BRCA 驱动疾病的临床迹象，但所有上述创始等位基因均为阴性。这一分析在 54/282（19.1%）BC、50/472（10.6%）OC 和 13/31（42%）BC+OC 患者中发现了额外的 BRCA1 或 BRCA2 突变携带者。对不同临床亚组（BC 与 OC 与 BC+OC；家族史阳性与阴性；早发与晚发；无单一或多个 BRCA1 或 BRCA2 相关疾病的临床指标）中创始和“罕见”BRCA1 和 BRCA2 致病性等位基因频率的分析表明，全面的 BRCA1 和 BRCA2 分析使所有受检女性的鉴定突变携带者数量增加了一倍以上。
强烈建议斯拉夫人群进行全长 BRCA1 和 BRCA2 测序，他们有进行 BRCA1 和 BRCA2 检测的医学指征，但对常见的 BRCA1 和 BRCA2 突变呈阴性。
