DOI: 10.6084/m9.figshare.28705609
title: Germline variants analysis of Chinese breast cancer patients reveals numerous alterations in homologous recombination genes

description: We aimed to identify the pathogenic variants of homologous recombination (HR) genes and analyze the correlation between the pathogenic variants and clinical characteristics in Chinese breast cancer patients. A cohort of 178 breast cancer patients participated in this study. We assessed genomic alterations using a 23-gene panel, which includes most of the HR-related genes and DNA mismatch repair (MMR) gene, through next-generation sequencing. The pathogenicity of variants was determined based on the American College of Medical Genetics and Genomics standards and guidelines. The correlation between these pathogenic variants and the clinical characteristics of the patients was investigated. 26 pathogenic variants, including one novel suspected pathogenic variant, were detected in 28 (15.7%) patients. These variants occurred in 7 HR-related genes: <i>BRCA1</i>, <i>BRCA2</i>, <i>PALB2</i>, <i>RAD51D</i>, <i>RAD50</i>, <i>BRIP1,</i> and <i>ATM</i>. The frequency of <i>BRCA1</i> variants was higher in the younger group (8.9%) compared to the older group (2.6%), while the trend was reversed for <i>BRCA2</i> (3.0% vs. 7.8%). All three patients with the pathogenic variant (p.Lys91fs) in <i>RAD51D</i> were diagnosed with triple-negative breast cancer. HR-gene testing in breast cancer could help to find new suspected pathogenic variants and increase the clinical benefit of multi-gene testing for breast cancer. Breast cancer is the most common cancer among women in China. Effective control is needed to decrease the effects and costs of this disease. Our study investigated the genetic reasons causing breast cancer in Chinese breast cancer patients using blood to find the causing genes based on known 23 genes associated with breast cancer. Our goal was to find out the genetic factors in Chinese breast cancer patients and evaluate the clinical value of this testing method. By improving early discovery and personalized care, this approach aims to help reduce breast cancer deaths in China. This study investigates the germline pathogenic variants of HR genes using next-generation sequencing in Chinese breast cancer patients.26 pathogenic variants were detected in 15.7% of patients, occurring in <i>BRCA1</i>, <i>BRCA2</i>, <i>PALB2</i>, <i>RAD51D</i>, <i>RAD50</i>, <i>BRIP1,</i> and <i>ATM</i>.A previously unreported deleterious variant (p.Leu304fs) in <i>PALB2</i> (NM_024675) was identified.The investigation highlights the value of HR-gene panel testing in Chinese breast cancer patients. This study investigates the germline pathogenic variants of HR genes using next-generation sequencing in Chinese breast cancer patients. 26 pathogenic variants were detected in 15.7% of patients, occurring in <i>BRCA1</i>, <i>BRCA2</i>, <i>PALB2</i>, <i>RAD51D</i>, <i>RAD50</i>, <i>BRIP1,</i> and <i>ATM</i>. A previously unreported deleterious variant (p.Leu304fs) in <i>PALB2</i> (NM_024675) was identified. The investigation highlights the value of HR-gene panel testing in Chinese breast cancer patients.