Assessing the Mutational Spectrum and Prevalence of Breast Cancer Risk Genes in an Unselected Hispanic Breast Cancer Cohort Using Population Genetic and Genomic Approaches
Author: Anna Marie de Asis Tuazon
Publisher:
Published: 2017
Total Pages:
ISBN-13: 9781369795776
DOWNLOAD EBOOKBreast cancer is the leading cause of cancer incidence and mortality among Hispanic women. The research described here aimed to assess the mutation prevalence in three breast cancer genes (BRCA1, BRCA2 and PALB2) in unselected Hispanic breast cancer cases. Unselected cases with invasive breast cancer, recruited through a multi-center study in Colombia, were screened for BRCA1/2 and PALB2 mutations using genotyping and Illumina sequencing. Analyses focused on mutation prevalence and clinical characteristics of the mutation carriers. We identified 67 cases with a pathogenic or likely-pathogenic mutation in BRCA1 (n=42), BRCA2 (n=18), and PALB2 (n=7). Eighty-eight percent of these mutations were founder mutations. Remarkably, we found that 10.4% of the cohort, regardless of family history of cancer, carried a pathogenic mutation. The high mutation prevalence in this cohort, and the lack of family history in >60% of the mutation carriers, suggests that population-based genetic analysis can identify most Hispanic carriers who would otherwise be ineligible for testing. Additionally, among the high prevalence of founder mutations was the BRCA1 c.3331_3334delCAAG mutation. This particular mutation has been reported previously in other parts of the world. Mutation carriers from Colombia, Spain, Portugal, Brazil, Chile, and Angola, were subjected to haplotype analysis. Significantly, mutation carriers from these diverse countries share a common core haplotype, likely originating from Iberia (Spain and Portugal). The estimated age of the mutation in Colombia and Spain was consistent with the European colonization, and this story illustrates trans-continental immigration of an important breast cancer-associated mutation, highlighting the significance of studying diverse populations.
