Role of non-coding sequence variants in cancer

Nature Reviews. Genetics
Ekta KhuranaMark Gerstein

Abstract

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.

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