Biomedical Genomics and Oncogenetics Research Laboratory, Faculty of Sciences and Techniques of Tangier, University Abdelmalek Essaâdi, P.A: 416-Tangier, Tangier, Morocco.
Oncology Clinic Al AMAL of Tangier, Tangier, Morocco.
BMC Cancer. 2020 Sep 7;20(1):859. doi: 10.1186/s12885-020-07352-9.
To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco.
Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform.
Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer.
Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.
迄今为止，BRCA1/2 突变在摩洛哥早发性乳腺癌患者中的作用仍不清楚。在此，我们首次在摩洛哥北部的队列中评估这些遗传改变。
招募了 33 名≤40 岁诊断为乳腺癌的患者，无论其是否有乳腺癌和/或卵巢癌家族史。使用 Ion Proton（Thermo Fisher Scientific）下一代测序平台，从外周血 DNA 中对 BRCA1 和 BRCA2 基因的编码区和内含子-外显子边界进行测序。
总体而言，鉴定出 5 个 BRCA 种系突变（15.1%）。有乳腺癌家族史的患者中突变的频率为 16.7%。在 BRCA1 中发现了 3 个突变（9%），BRCA2 基因中有 2 个突变（6%）。这是 3 个移码突变（c.798_799del、c.2125_2126insA、c.5116_5119delAATA）、1 个错义突变（c.116G > A）和 1 个无义突变（c.289G > T）。c.5116_5119delAATA 在北非具有启动子效应。此外，在 BRCA2 中还发现了一个意义不明的变异体（c.4090A > G）。大多数 BRCA 突变携带者（80%）没有乳腺癌家族史。
我们的数据不支持 BRCA 突变单独解释摩洛哥年轻女性乳腺癌高发的假说。≤40 岁的乳腺癌诊断年龄似乎强烈预测摩洛哥患者的 BRCA 突变状态。这些结果将有助于在全国范围内做出遗传咨询和检测的决策。
