Mehemmai Chiraz, Cherbal Farid, Hamdi Yosr, Guedioura Abdelmoumene, Benbrahim Wassila, Bakour Rabah, Abdelhak Sonia
Unit of Genetics, Laboratory of Molecular and Cellular Biology, Faculty of Biological Sciences, USTHB, POB 32 El Alia, Bab Ezzouar, 16111, Algiers, Algeria.
Faculty of Sciences of Tunis, University Campus 2092 - El Manar, Tunis, University of Tunis El Manar, Tunis, Tunisia.
Pathol Oncol Res. 2020 Apr;26(2):715-726. doi: 10.1007/s12253-019-00586-4. Epub 2019 Feb 4.
Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. In this study, we aimed to investigate the mutation spectrum of BRCA1 and BRCA2 genes in hereditary breast/ovarian cancer (HBOC) families from the Aures region (eastern Algeria). High risk breast/ovarian cancer families were selected from overall 1162 consecutive patients collected from cancer registry of anticancer center of Batna. Breast cancers were diagnosed between 2011 and 2015. Recurrent mutations on BRCA1 and BRCA2 previously found in Algerian patients were screened using PCR-direct sequencing in 113 HBOC families. In addition, for the first time in Algeria, HBOC patients were analyzed by NGS using a cancer panel of 30 hereditary cancer genes or BRCA1/2 genetic test. Six distinct deleterious mutations in BRCA1 and BRCA2 and a new VUS in PALB2 were detected in ten patients. Two distinct BRCA2 pathogenic variants c.1813dupA and c.8485C > T detected in two young female triple negative breast cancer (TNBC) patients, respectively, with a family history of male breast cancer, are reported here for the first time in Algerian population. Interestingly, we also detected a BRCA exon 15 deletion in two unrelated young female TNBC patients with strong family history of breast/ovarian cancer. Our study showed differences in the distribution of the mutation spectrum of BRCA genes between the Aures region and the north central region of Algeria. Our results will contribute in the implementation of genetic counseling and testing for patients and families at risk of hereditary breast and ovarian cancer.
乳腺癌目前是阿尔及利亚女性癌症发病和死亡的主要原因。在本研究中，我们旨在调查来自奥雷斯地区（阿尔及利亚东部）的遗传性乳腺癌/卵巢癌（HBOC）家族中BRCA1和BRCA2基因的突变谱。从巴特纳抗癌中心癌症登记处收集的1162例连续患者中选取高风险乳腺癌/卵巢癌家族。乳腺癌诊断时间为2011年至2015年。在113个HBOC家族中，使用PCR直接测序法筛查先前在阿尔及利亚患者中发现的BRCA1和BRCA2的复发性突变。此外，在阿尔及利亚首次使用包含30个遗传性癌症基因的癌症检测板或BRCA1/2基因检测对HBOC患者进行了二代测序分析。在10名患者中检测到BRCA1和BRCA2的6种不同的有害突变以及PALB2中的一种新的意义未明的变异（VUS）。分别在两名患有男性乳腺癌家族史的年轻女性三阴性乳腺癌（TNBC）患者中检测到两种不同的BRCA2致病变体c.1813dupA和c.8485C>T，这在阿尔及利亚人群中尚属首次报道。有趣的是，我们还在两名有强烈乳腺癌/卵巢癌家族史的无血缘关系的年轻女性TNBC患者中检测到BRCA外显子15缺失。我们的研究显示了阿尔及利亚奥雷斯地区与中北部地区BRCA基因突变谱分布的差异。我们的结果将有助于为有遗传性乳腺癌和卵巢癌风险的患者及家族开展遗传咨询和检测。
