Kwoneel Kim1,3, Kiwon Jang1,3, Woojin Yang1,3, Eun-Young Choi2, Seong-Min Park2, Mingyun Bae1,2, Youn-Jae Kim2 & Jung Kyoon Choi1,*
1Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea. 2Specific Organs Cancer Branch, Research Institute, National Cancer Center, Gyeonggi, Republic of Korea. 3These authors contributed equally to this work.
*Correspondence to : Jung Kyoon Choi
Recurrence is a hallmark of cancer-driving mutations. Recurrent mutations can arise at the same site or affect the same gene at different sites. Here we identified a set of mutations arising in individual samples and altering different cis-regulatory elements that converge on a common gene via chromatin interactions. The mutations and genes identified in this fashion showed strong relevance to cancer, in contrast to noncoding mutations with site-specific recurrence only. We developed a prediction method that identifies potentially recurrent mutations on the basis of the features shared by mutations whose recurrence is observed in a given cohort. Our method was capable of accurately predicting recurrent mutations at the level of target genes but not mutations recurring at the same site. We experimentally validated predicted mutations in distal regulatory regions of the TERT gene. In conclusion, we propose a novel approach to discovering potential cancer-driving mutations in noncoding regions.