Work

The landscape of somatic mutations in protein coding genes in apparently benign human tissues carries signatures of relaxed purifying selection

Year: 2016

Type: article

Abstract: Mutations acquired during development and aging lead to inter- and intra-tissue genetic variations. Evidence linking such mutations to complex traits and diseases is rising. We detected somatic mutations in protein-coding regions in 140 benign tissue samples representing nine tissue-types (bladder, breast, liver, lung, prostate, stomach, thyroid, head and neck) and paired blood from 70 donors. A total of 80% of the samples had 2-39 mutations detectable at tissue-level resolution. Factors such as age and smoking were associated with increased burden of detectable mutations, and tissues carried signatures of distinct mutagenic processes such as oxidative DNA damage and transcription-coupled repair. Using mutational signatures, we predicted that majority of the mutations in blood originated in hematopoietic stem and early progenitor cells. Missense to silent mutations ratio and the persistence of potentially damaging mutations in expressed genes carried signatures of relaxed purifying selection. Our findings have relevance for etiology, diagnosis and treatment of diseases including cancer.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkw086

Authors: Vinod Kumar Yadav, James DeGregori, Subhajyoti De

Institutions: University of Colorado Anschutz, University of Colorado Cancer Center, University of Colorado Denver, Colorado School of Public Health

Language: English

Topic: Cancer Genomics and Diagnostics

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,992