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Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients
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Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients
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Journal Article
Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients
2019
Overview
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.
Activating oncogenic mutations in
KRAS
and
NRAS
are common in colorectal cancer, which is a heterogenous disease. Here, the authors show that the
RAS
mutation spectrum is markedly different between colon and rectal cancer, and also different based on age of diagnosis and microsatellite instability.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Cancer
/ Codons
/ Colon
/ Colonic Neoplasms - genetics
/ Female
/ Genetic Variation - genetics
/ GTP Phosphohydrolases - genetics
/ Humanities and Social Sciences
/ Humans
/ Male
/ Membrane Proteins - genetics
/ Mutation
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Rectum
/ Science
/ Structure-Activity Relationship
/ Structure-function relationships
/ Tumors
