Genome Instability in Blood Cells of a BRCA1+ Breast Cancer Family

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2014 Jun 3

PMID 24884718

Citations 4

Authors

Fengxia Xiao

Yeong C Kim

Carrie Snyder

Hongxiu Wen

Pei Xian Chen

Jiangtao Luo

Dina Becirovic

Bradley Downs

Kenneth H Cowan

Henry Lynch

San Ming Wang

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

Citing Articles

The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers.

Oubaddou Y, Ben Ali F, Oubaqui F, Qmichou Z, Bakri Y, Ameziane El Hassani R Asian Pac J Cancer Prev. 2023; 24(9):3139-3153.

PMID: 37774066 PMC: 10762740. DOI: 10.31557/APJCP.2023.24.9.3139.

Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer.

Du X, Yang X, Wang Q, Lin G, Li P, Zhang W Heliyon. 2023; 9(2):e13185.

PMID: 36747547 PMC: 9898304. DOI: 10.1016/j.heliyon.2023.e13185.

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals.

Williams K, Lemieux G, Hassis M, Olshen A, Fisher S, Werb Z Proc Natl Acad Sci U S A. 2016; 113(10):E1343-51.

PMID: 26903627 PMC: 4790982. DOI: 10.1073/pnas.1600645113.

BPTF Associated with EMT Indicates Negative Prognosis in Patients with Hepatocellular Carcinoma.

Xiao S, Liu L, Fang M, Zhou X, Peng X, Long J Dig Dis Sci. 2014; 60(4):910-8.

PMID: 25362514 DOI: 10.1007/s10620-014-3411-0.

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