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

Role of non-coding sequence variants in cancer.

Khurana E1,2,3,4, Fu Y5, Chakravarty D2,6, Demichelis F2,3,7, Rubin MA1,2,6, Gerstein M8,9,10.

Author information

1
Meyer Cancer Center, Weill Cornell Medical College, New York, New York 10065, USA.
2
Institute for Precision Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
3
Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York 10021, USA.
4
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.
5
Bina Technologies, Roche Sequencing, Redwood City, California 94065, USA.
6
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
7
Centre for Integrative Biology, University of Trento, 38123 Trento, Italy.
8
Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
9
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
10
Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA.

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.

PMID:
26781813
DOI:
10.1038/nrg.2015.17
[Indexed for MEDLINE]

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