Role of non-coding sequence variants in cancer

Nat Rev Genet. 2016 Feb;17(2):93-108. doi: 10.1038/nrg.2015.17. Epub 2016 Jan 19.


Patients with cancer carry somatic sequence variants in their tumour in addition to the germline variants in their inherited genome. Although variants in protein-coding regions have received the most attention, numerous studies have noted the importance of non-coding variants in cancer. Moreover, the overwhelming majority of variants, both somatic and germline, occur in non-coding portions of the genome. We review the current understanding of non-coding variants in cancer, including the great diversity of the mutation types--from single nucleotide variants to large genomic rearrangements--and the wide range of mechanisms by which they affect gene expression to promote tumorigenesis, such as disrupting transcription factor-binding sites or functions of non-coding RNAs. We highlight specific case studies of somatic and germline variants, and discuss how non-coding variants can be interpreted on a large-scale through computational and experimental methods.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Regulation, Neoplastic
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genomic Instability
  • Germ-Line Mutation
  • Humans
  • Neoplasms / genetics*
  • RNA, Untranslated*


  • RNA, Untranslated