Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients

Ilya G. Serebriiskii, Caitlin Connelly, Garrett Frampton, Justin Newberg, Matthew Cooke, Vince Miller, Siraj Ali, Jeffrey S. Ross, Elizabeth Handorf, Sanjeevani Arora, Christopher Lieu, Erica A. Golemis and Joshua E. Meyer ()
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Ilya G. Serebriiskii: Fox Chase Cancer Center
Caitlin Connelly: Foundation Medicine Inc.
Garrett Frampton: Foundation Medicine Inc.
Justin Newberg: Foundation Medicine Inc.
Matthew Cooke: Foundation Medicine Inc.
Vince Miller: Foundation Medicine Inc.
Siraj Ali: Foundation Medicine Inc.
Jeffrey S. Ross: Foundation Medicine Inc.
Elizabeth Handorf: Fox Chase Cancer Center
Sanjeevani Arora: Fox Chase Cancer Center
Christopher Lieu: University of Colorado Cancer Center
Erica A. Golemis: Fox Chase Cancer Center
Joshua E. Meyer: Fox Chase Cancer Center

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11530-0

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