BRCA1, BRCA2, TP53, PIK3CA, PTEN and AKT1 genes mutations in Burkina Faso breast cancer patients: prevalence, spectrum and novel variant

• Published in: Molecular genetics and genomics : MGG Vol. 297; no. 5; pp. 1257 - 1268
• Main Authors: Ouedraogo, Serge Yannick, Zoure, Abdou Azaque, Zeye, Moutanou Modeste Judes, Kiendrebeogo, Touwendpoulimdé Isabelle, Zhou, Xi, Sawadogo, Alexis Yobi, Simpore, Jacques, Chen, Hanchun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022; Springer Nature B.V
• Subjects: AKT1 protein; Animal Genetics and Genomics; Biochemistry; Biomedical and Life Sciences; BRCA1 protein; BRCA2 protein; Breast cancer; breast neoplasms; Burkina Faso; Chemotherapy; drug therapy; ErbB-2 protein; exons; genomics; germ cells; Human Genetics; Life Sciences; Microbial Genetics and Genomics; Mutation; Original Article; p53 Protein; Patients; Plant Genetics and Genomics; Population; PTEN protein; surgery; Tumor suppressor genes; tumor suppressor proteins; Tumors; Burkina Faso; Pathogenic variant; Prevention; Breast cancer; Burkina Faso; Sanger sequencing
• ISSN: 1617-4615; 1617-4623; 1617-4623
• DOI: 10.1007/s00438-022-01914-1

BRCA1 and BRCA2 are the two most commonly mutated tumor suppressor genes associated with hereditary breast cancer (BC). Also, mutations in TP53, PIK3CA, PTEN and AKT1 were observed at a high frequency in BC with their mutation spectrum exhibiting a subgroup particularity with enormous clinical significance in the prevention, classification and treatment of cancers. Unfortunately, the mutation spectrum of these genes is still unknown in most Sub-Saharan African population. Therefore, using samples from 133 unselected BC patients, we aimed to assess the contribution of these mutations by direct Sanger sequencing. The analysis revealed pathogenic germline variants on BRCA1 exon 11 (c.3331C > T, 0.75%) and BRCA2 exon 11 (c.5635G > T, c.6211delA; 1.5%). Five other pathogenic variants were identified in 61 of the 133 subjects (45.86%), with 39.09% for PIK3CA , 12.78% for TP53 . Interestingly, a variant in PIK3CA found in high frequency in our population was different from the one usually found in other populations (c.1634A > C, 38.34%), and four patients carried mutations linked to Cowen Syndrome 5 c.[1634A > C;1658_1659delGTinsC]. A novel variant (c.312G > T) was found in TP53 gene at 12.78%. Overall, mutation carriers were found more in Her2 negative and in patients that underwent surgery and chemotherapy. No pathogenic variant was found in PTEN and AKT1 . Our population displayed a high frequency of PIK3CA mutations with an unusual distribution and spectrum as well as a relatively low prevalence of BRCA mutations. Our results provided novel data on an unstudied population and may help in prevention, and the establishment of suitable therapeutic approaches for our population.