학술논문
CTCF/cohesin-binding sites are frequently mutated in cancer.
Document Type
Article
Author
Katainen, Riku; Pitkänen, Esa; Palin, Kimmo; Välimäki, Niko; Gylfe, Alexandra E; Ristolainen, Heikki; Hänninen, Ulrika A; Cajuso, Tatiana; Kondelin, Johanna; Tanskanen, Tomas; Kaasinen, Eevi; Kilpivaara, Outi; Tuupanen, Sari; Aaltonen, Lauri A; Dave, Kashyap; Enge, Martin; Kivioja, Teemu; Mecklin, Jukka-Pekka; Järvinen, Heikki; Lepistö, Anna
Source
Subject
*COHESINS
*GENETICS of colon cancer
*GENOMICS
*EXONUCLEASES
*HOMEOSTASIS
*GENETIC mutation
*
*
*
*
*
Language
ISSN
1061-4036
Abstract
Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome. [ABSTRACT FROM AUTHOR]