Capturing the primordial Kras mutation initiating urethane carcinogenesis.

Journal Article (Journal Article)

The environmental carcinogen urethane exhibits a profound specificity for pulmonary tumors driven by an oncogenic Q61L/R mutation in the gene Kras. Similarly, the frequency, isoform, position, and substitution of oncogenic RAS mutations are often unique to human cancers. To elucidate the principles underlying this RAS mutation tropism of urethane, we adapted an error-corrected, high-throughput sequencing approach to detect mutations in murine Ras genes at great sensitivity. This analysis not only captured the initiating Kras mutation days after urethane exposure, but revealed that the sequence specificity of urethane mutagenesis, coupled with transcription and isoform locus, to be major influences on the extreme tropism of this carcinogen.

Full Text

Duke Authors

Cited Authors

  • Li, S; MacAlpine, DM; Counter, CM

Published Date

  • April 14, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 1800 -

PubMed ID

  • 32286309

Pubmed Central ID

  • PMC7156420

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-15660-8


  • eng

Conference Location

  • England