Abstract

A Cohort Study of Early Onset Breast Cancer

Kuo Ping Chiu, Associate Research Fellow, Academia Sinica

Early onset breast cancer (EOBC) occurs in young women at 40-year-old or younger, and is typically more aggressive than those diagnosed at later ages. Its underlying etiology is unclear. We analyzed whole exome sequencing data generated from the WBC and tumor tissues of 86 patients diagnosed with EOBC, focusing on somatic nonsynonymous mutations (SNMs) in tumor tissue and the germline mutations (GMs). For the former, we calculated the base composition for all genomic locations after mapping all libraries against hg19 and compared the alterations from WBC to tumor in base composition. We then used the criteria WBC-wtp (wild-type) > 75% and Tumor-v (variant) > 20% to screen in-patient SNMs, which contained the newly acquired subset (WBC-wtp = 100%). For the latter, we compared WBC sequences against hg19 and all available databases, including 1,000 genomes, COSMIC, and METABRIC. We studied the alterations at both the gene-level and the pathway level. Results indicated that the TOP 20 genes with highest occurrences of SNMs among the 86 EOBC patients are mainly cellar structural proteins, secretory proteins, or proteins with detoxification functions. Pathway analysis indicated a potential defect in immune system. We have also identified some novel genes associated with EOBC which are not reported previously.