An In Vivo Kras Allelic Series Reveals Distinct Phenotypes of Common Oncogenic Variants.

ABSTRACT: KRAS is the most frequently mutated oncogene in cancer, yet there is little understanding of how specific KRAS amino acid changes affect tumor initiation, progression, or therapy response. Using high-fidelity CRISPR-based engineering, we created an allelic series of new LSL-Kras mutant mice, reflecting codon 12 and 13 mutations that are highly prevalent in lung (KRAS^G12C), pancreas (KRAS^G12R), and colon (KRAS^G13D) cancers. Induction of each allele in either the murine colon or pancreas revealed striking quantitative and qualitative differences between KRAS mutants in driving the early stages of transformation. Furthermore, using pancreatic organoid models, we show that KRAS^G13D mutants are sensitive to EGFR inhibition, whereas KRAS<

SUBMITTER: Zafra MP 

PROVIDER: S-EPMC7642097 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature