Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas.

ABSTRACT:

Background & aims

Little is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of function mutations (nonsense and splice site) in genes that regulate OIS: the p16-Rb and ATM-ATR DNA damage response pathways.

Methods

Through a bioinformatic analysis of the literature, we identified a set of genes that function at the main nodes of

SUBMITTER: Gala MK 

PROVIDER: S-EPMC3978775 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature