BackgroundBreast cancer is one of the most prevalent malignancies in the world. In Peru, breast cancer is the second cause of death among women. Five to ten percent of patients present a high genetic predisposition due to BRCA1 and BRCA2 germline mutations.MethodsWe performed a comprehensive analysis of BRCA1 and BRCA2 genes by Sanger sequencing and multiplex ligation‐dependent probe amplification (MLPA) to detect large rearrangements in patients from 18 families, which met the criteria for hereditary breast cancer.ResultsIn this series, we found four pathogenic mutations, three previously reported (BRCA1: c.302‐1G>C and c.815_824dup10; BRCA2: c.5946delT) and a duplication of adenines in exon 15 in BRCA1 gene (c.4647_4648dupAA, ClinVar SCV000256598.1). We also found two exonic and four intronic variants of unknown significance and 28 polymorphic variants.ConclusionThis is the first report to determine the spectrum of mutations in the BRCA1/BRCA2 genes in Peruvian families selected by clinical and genetic criteria. The alteration rate in BRCA1/BRCA2 with proven pathogenic mutation was 22.2% (4 out 18) and this finding could be influenced by the reduced sample size or clinical criteria. In addition, we found three known BRCA1/BRCA2 mutations and a BRCA1 c.4647_4648dupAA as a novel pathogenic mutation.
La evaluación genotóxica de un producto es un paso importante para determinar su viabilidad para consumo humano. Se ha elaborado una bebida experimental a base de pseudocereales de alto valor nutricional como son quinua (Chenopodium quinoa Willd.), kiwicha (Amaranthus caudatus L.) y kañiwa (Chenopodium pallidicaule Aellen), preparada para inducir un posible efecto hipolipemiante en un grupo de personas. El objetivo de este estudio fue evaluar el potencial genotóxico de esta bebida experimental mediante dos pruebas in vitro validadas por agencias internacionales. En la prueba de Ames se utilizaron las cepas TA98 y TA100 de Salmonella typhimurium, con y sin fracción microsomal (S9). Se evaluaron 4 dosis de bebida y además un posible efecto antimutagénico (mismas 4 dosis más mutágeno). Para la prueba de micronúcleos se usó cultivos de linfocitos con células binucleadas, en presencia de cinco dosis de la bebida. Ambas pruebas indican que la bebida estudiada en sus distintas dosis, no presenta efecto genotóxico. Sin embargo, en la evaluación del posible efecto protector de la bebida, se evidenciaría que por el contrario, se potencia el efecto mutagénico de los mutágenos empleados para cada cepa. Por lo tanto, es importante que esta bebida experimental sea sometida a pruebas adicionales in vitro e in vivo para evaluar el potencial genotóxico antes de su consumo.
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.302-1G>C 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.140G>T, in exon 5 of BRCA1 and c.464G>A and c.938C>T 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, Castañeda 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.
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