A PoleP286R mouse model of endometrial cancer recapitulates high mutational burden and immunotherapy response.

ABSTRACT: Cancer is instigated by mutator phenotypes, including deficient mismatch repair and p53-associated chromosomal instability. More recently, a distinct class of cancers was identified with unusually high mutational loads due to heterozygous amino acid substitutions (most commonly P286R) in the proofreading domain of DNA polymerase ε, the leading strand replicase encoded by POLE. Immunotherapy has revolutionized cancer treatment, but new model systems are needed to recapitulate high mutational burdens characterizing human cancers and permit study of mechanisms underlying clinical responses. Here, we show that activation of a conditional LSL-PoleP286R allele in endometrium is sufficient to elicit in all animals endometrial cancers closely resembling their human counterparts, including very hig

SUBMITTER: Li HD 

PROVIDER: S-EPMC7453891 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature