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Delineation of the Germline and Somatic Mutation Interaction Landscape in Triple-Negative and Non-Triple-Negative Breast Cancer.

Abstract：

Background:Breast cancer development and progression involve both germline and somatic mutations. High-throughput genotyping and next-generation sequencing technologies have enabled discovery of genetic risk variants and acquired somatic mutations driving the disease. However, the possible oncogenic interactions between germline genetic risk variants and somatic mutations in triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC) have not been characterized. Here, we delineated the possible oncogenic interactions between genes containing germline and somatic mutations in TNBC and non-TNBC and investigated whether there are differences in gene expression and mutation burden between the two types of breast cancer. Methods:We addressed this problem by integrating germline mutation information from genome-wide association studies with somatic mutation information from next-generation sequencing using gene expression data as the intermediated phenotype. We performed network and pathway analyses to discover molecular networks and signalling pathways enriched for germline and somatic mutations. Results:The investigation revealed signatures of differentially expressed and differentially somatic mutated genes between TNBC and non-TNBC. Network and pathway analyses revealed functionally related genes interacting in gene regulatory networks and multiple signalling pathways enriched for germline and somatic mutations for each type of breast cancer. Among the signalling pathways discovered included the DNA repair and Androgen and ATM signalling pathways for TNBC and the DNA damage response, molecular mechanisms of cancer, and ATM and GP6 signalling pathways for non-TNBC. Conclusions:The results show that integrative genomics is a powerful approach for delineating oncogenic interactions between genes containing germline and genes containing somatic mutations in TNBC and non-TNBC and establishes putative functional bridges between genetic and somatic alterations and the pathways they control in the two types of breast cancer.

journal_name

Int J Genomics

journal_title

International journal of genomics

authors

Wu J,Mamidi TKK,Zhang L,Hicks C

doi

10.1155/2020/2641370

subject

Has Abstract

pub_date

2020-07-06 00:00:00

pages

2641370

eissn

2314-436X

issn

2314-4378

journal_volume

2020

pub_type

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Delineation of the Germline and Somatic Mutation Interaction Landscape in Triple-Negative and Non-Triple-Negative Breast Cancer.