Deep Genetic Connection Between Cancer and Developmental Disorders. Issue 10 (23rd August 2016)

• Record Type: Journal Article
• Authors: Qi, Hongjian; Dong, Chengliang; Chung, Wendy K.; Wang, Kai; Shen, Yufeng
• Is Part Of: Human mutation. Volume 37:Issue 10(2016)
• Page Start: 1042
• Page End: 1050
• Publication Date: 2016-08-23
• Subjects: developmental disorders -- de novo mutations -- somatic mutation hotspots -- tumor suppressors; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23040
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract : We quantified the genetic connection between cancer and developmental disorders (DD) using large‐scale exome sequencing data, and found that at least a third of DD risk genes are cancer drivers, and these genes often had similar mode of action in cancer and DD. As a result, germline missense de novo mutations located in cancer mutation hotspots are more likely to be implicated with DD. Our findings suggest that cancer genomics data can be used to improve DD risk gene discovery. ABSTRACT: Cancer and developmental disorders (DDs) share dysregulated cellular processes such as proliferation and differentiation. There are well‐known genes implicated in both in cancer and DDs. In this study, we aim to quantify this genetic connection using publicly available data. We found that among DD patients, germline damaging de novo variants are more enriched in cancer driver genes than non‐drivers. We estimate that cancer driver genes comprise about a third of DD risk genes. Additionally, de novo likely‐gene‐disrupting variants are more enriched in tumor suppressors, and about 40% of implicated de novo damaging missense variants are located in cancer somatic mutation hotspots, indicating that many genes have a similar mode of action in cancer and DDs. Our results suggest that we can view tumors as natural laboratories for assessing the deleterious effects of mutations that are applicable to germline variants and identification of causal genes and variants in DDs.