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Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients
Serebriiskii, Ilya G. Connelly, Caitlin Frampton, Garrett Newberg, Justin Cooke, Matthew Miller, Vince Ali, Siraj Ross, Jeffrey S. Handorf, Elizabeth A. Arora, Sanjeevani
Serebriiskii, Ilya G.
Connelly, Caitlin
Frampton, Garrett
Newberg, Justin
Cooke, Matthew
Miller, Vince
Ali, Siraj
Ross, Jeffrey S.
Handorf, Elizabeth A.
Arora, Sanjeevani
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Journal article
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2019-08-19
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Cancer and Cellular Biology
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http://dx.doi.org/10.1038/s41467-019-11530-0
Abstract
Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS, NRAS, and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.
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Serebriiskii IG, Connelly C, Frampton G, Newberg J, Cooke M, Miller V, et al. Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients. Nat Commun. 2019 Aug 19;10:3722. doi:10.1038/s41467-019-11530-0.
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Nature Research
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Nature Communications, Vol. 10
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