Format

Send to

Choose Destination
Nat Rev Cancer. 2018 Dec;18(12):767-777. doi: 10.1038/s41568-018-0076-6.

A model for RAS mutation patterns in cancers: finding the sweet spot.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
2
Helen Diller Family Comprehensive Cancer Center and Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
3
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA. count004@mc.duke.edu.

Abstract

The three RAS genes - HRAS, NRAS and KRAS - are collectively mutated in one-third of human cancers, where they act as prototypic oncogenes. Interestingly, there are rather distinct patterns to RAS mutations; the isoform mutated as well as the position and type of substitution vary between different cancers. As RAS genes are among the earliest, if not the first, genes mutated in a variety of cancers, understanding how these mutation patterns arise could inform on not only how cancer begins but also the factors influencing this event, which has implications for cancer prevention. To this end, we suggest that there is a narrow window or 'sweet spot' by which oncogenic RAS signalling can promote tumour initiation in normal cells. As a consequence, RAS mutation patterns in each normal cell are a product of the specific RAS isoform mutated, as well as the position of the mutation and type of substitution to achieve an ideal level of signalling.

PMID:
30420765
DOI:
10.1038/s41568-018-0076-6
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center