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December 05-06, 2019 | Dubai, UAE

International Conference on

Nursing Education and Research

Cancer and Cancer Therapy

Joint Event

Journal of Medical Oncology and Therapeutics | Volume 4

RAS mutation tropism

Christopher M Counter, Siqi Li

and

David MacAlpine

Duke University Medical Center, USA

ncogenic mutations in HRAS, NRAS and KRAS commonly

occur in a wide spectrum of human cancers. These

mutations are not uniformbut instead have a tropism, namely

the frequency, RAS isoform, position and type of mutation are

often unique to each cancer. There is no definitivemechanism

to explain this clinical finding, although the pattern itself has

been widely reported for decades. As oncogenic RAS can

induce tumorigenesis, the mutation tropism of these genes

must underlie some fundamental feature of tumor initiation,

or to put it another way, how cancer arises. Determining how

specific RAS mutations occur would thus shed light on the

process of cancer initiation, which has clinical implications

for early detection and perhaps even preventative measures.

This phenomenon is recapitulated in mice exposed to

the environmental carcinogen urethane, which develop

KrasQ61L/R-mutant pulmonary tumors, making urethane

carcinogenesis an ideal platform to elucidate the underlying

principles of RAS mutation tropism. To this end, we adapted

the error-corrected, high-throughput sequencing approach

of maximum depth sequencing to detect mutations in

the endogenous murine Kras gene at great sensitivity in

vivo, capturing the initiating mutations following urethane

exposure. Further, by sequencing Kras as well as Hras in

this manner and from different tissues and over time, we

find that the sequence specificity of urethane mutagenesis,

coupled with Kras transcription, to bemajor influences on the

extreme tropism of this carcinogen.

J Med Oncl Ther| Volume 4