Distinct Patterns of Somatic Mosaicism in the APC Gene in Neoplasms From Patients With Unexplained Adenomatous Polyposis

Gastroenterology. 2017 Feb;152(3):546-549.e3. doi: 10.1053/j.gastro.2016.10.040. Epub 2016 Nov 2.

Abstract

We investigated the presence and patterns of mosaicism in the APC gene in patients with colon neoplasms not associated with any other genetic variants; we performed deep sequence analysis of APC in at least 2 adenomas or carcinomas per patient. We identified mosaic variants in APC in adenomas from 9 of the 18 patients with 21 to approximately 100 adenomas. Mosaic variants of APC were variably detected in leukocyte DNA and/or non-neoplastic intestinal mucosa of these patients. In a comprehensive sequence analysis of 1 patient, we found no evidence for mosaicism in APC in non-neoplastic intestinal mucosa. One patient was found to carry a mosaic c.4666dupA APC variant in only 10 of 16 adenomas, indicating the importance of screening 2 or more adenomas for genetic variants.

Keywords: Wnt signaling; colorectal carcinogenesis; mutation; unexplained polyposis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenomatous Polyposis Coli / genetics*
  • Adult
  • Aged
  • Carcinoma / genetics*
  • Colorectal Neoplasms / genetics*
  • Female
  • Genes, APC*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mosaicism*
  • Neoplasms, Multiple Primary / genetics*
  • Sequence Analysis, DNA
  • Wnt Signaling Pathway