Open Access Highly Accessed Research article

Genome instability in blood cells of a BRCA1+ breast cancer family

Fengxia Xiao1, Yeong C Kim1, Carrie Snyder2, Hongxiu Wen1, Pei Xian Chen3, Jiangtao Luo4, Dina Becirovic2, Bradley Downs1, Kenneth H Cowan5, Henry Lynch2* and San Ming Wang1*

Author Affiliations

1 Department of Genetics, Cell Biology and Anatomy, Omaha, NE 68198, USA

2 Hereditary Cancer Center, Department of Preventive Medicine, Creighton University, Omaha, NE 68198, USA

3 Department of Medicine, College of Medicine, Omaha, NE 68178, USA

4 Department of Biostatistics, College of Public Health, Omaha, NE 68178, USA

5 Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68178, USA

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BMC Cancer 2014, 14:342  doi:10.1186/1471-2407-14-342

Published: 19 May 2014



BRCA1 plays an essential role in maintaining genome stability. Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition leading to high risk of breast cancer. While BRCA1+ induces breast cancer by causing genome instability, most of the knowledge is known about somatic genome instability in breast cancer cells but not germline genome instability.


Using the exome-sequencing method, we analyzed the genomes of blood cells in a typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation, including six breast cancer-affected and two breast cancer unaffected members.


We identified 23 deleterious mutations in the breast cancer-affected family members, which are absent in the unaffected members. Multiple mutations damaged functionally important and breast cancer-related genes, including transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations between the mothers and daughters shows that most mutations were germline mutation inherited from the ancestor(s) while only a few were somatic mutation generated de novo.


Our study indicates that BRCA1+ can cause genome instability with both germline and somatic mutations in non-breast cells.

BRCA1+; Familial breast cancer; Exome sequencing; Bioinformatics; Germline mutation; Genome instability