Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1^+/--driven murine colonic adenomas.

ABSTRACT:

Background

The loss of a single copy of adenomatous polyposis coli (Apc) in leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1)-expressing colonic progenitor cells induces rapid growth of adenomas in mice with high penetrance and multiplicity. The tumors lack functional APC, and a genetic loss of heterozygosity of Apc was previously observed.

Methods

To identify genomic features of early tumorigenesis, and to profile intertumoral genetic heterogeneity, tumor exome DNA (n = 9 tumors) and mRNA (n = 5 tumors) sequences were compared with matched nontumoral colon tissue. Putative somatic mutations were called after stringent variant filtering. Somatic signatures of mutational processes were determined and splicing patterns were observed.

Results

The adenomas we

SUBMITTER: Preston JL 

PROVIDER: S-EPMC7023705 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature