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Intestinal cancer modifier MeDIP-Seq

ABSTRACT: Cancers predominantly arise from adult stem cells accumulating somatic driver mutations, but how genetic predisposition affects the penetrance of mutations in tumor initiation is not well understood. Here, we have analyzed gene expression in tumor-prone ApcMin/+ mice on highly variant C57BL/6J and PWD/Ph genetic backgrounds. We show that activation of beta-Catenin-driven and stem cell-specific gene expression in the presence of ApcMin or following APC loss is high in B6 mouse intestines, but remains moderate in intestines carrying PWD/Ph chromosome 5, suggesting that PWD/Ph variants restrict adenoma initiation by controlling stem cell homeostasis. Gene expression of modifier candidates and DNA methylation on chromosome 5 are predominantly cis-controlled and largely reflect the parental patterns, providing a genetic basis for inheritance of tumor susceptibility.

ORGANISM(S): Mus musculus

PROVIDER: GSE148369 | GEO | 2023/03/20

REPOSITORIES: GEO

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