Molecular Evaluation Of Peruvian Patients With Hereditary Breast Cancer Reveals A Novel Germline Mutation In Brca1

Background Breast cancer is the leading cancer in women worldwide, while in Peru is the second most frequent cancer with a high incidence of triple negative breast cancers (21%). There is no previous information about BRCA1/BRCA2 mutations in Peruvian high-risk breast cancer patients. Prior studies from International diagnostic laboratories only presented results of our population as a pooled Hispanic data. Our aim was to characterize mutations in BRCA1/BRCA2 genes in Peruvian patients with breast cancer with hereditary patterns. Methods We evaluated mutations in BRCA1/BRCA2 genes by Sanger sequencing and large genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA) in 18 families with hereditary breast cancer criteria identified at the Breast Unit of Oncosalud-AUNA (Lima-Peru). Molecular analysis was done in the facilities of Genetics and Molecular Biology Center at the San Martin de Porres University (Lima-Peru). Results Sequencing identified 4 pathogenic mutations in 4/18 families, three previously detected ( BRCA1: c.302-1Gu003eC y c.815_824dup10; BRCA2: c.5946delT) and a novel germline mutation in exon 15 of BRCA1 (c.4647_4648dupAA, ClinVar SCV000256598.1) producing a frameshift variant. MLPA revealed 2 amplifications in exon 7 (duplication and triplication) in BRCA1 in unrelated patients with potential pathogenic effects, one of this co-existed with the BRCA2: c.5946delT mutation. In addition, three variants of uncertain significance were found (c.140Gu003eT, in exon 5 of BRCA1 and c.464Gu003eA and c.938Cu003eT in exon 5 and 10 of BRCA2 , respectively). Conclusions After a comprehensive evaluation we found an alteration rate of 27.8% (5/18) in BRCA1/BRCA2 in families with criteria for hereditary breast cancer. We reported BRCA1 c.4647_4648dupAA as a novel mutation. Further studies including a larger sample size of Peruvian patients should evaluate the prevalence or founder effect of this mutation in our population. Citation Format: Ponce J, Vigil C, Araujo JM, Castaneda C, Calderon G, Buleje JL, Acosta O, Danos P, Huaman F, Guevara-Fujita ML, Aguilar A, Pinto JA, Gomez HL, Fujita R. Molecular evaluation of Peruvian patients with hereditary breast cancer reveals a novel germline mutation in BRCA1 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-08.