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Scientific article
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English

Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue

Published inCell reports, vol. 19, no. 11, p. 2185-2192
Publication date2017-06
Abstract

The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apcmin/+ mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been acquired in vivo at the single-cell level. SNSs, most of them being CpG-to-TpG substitutions, were at least ten times more frequent in adenoma than normal cells. Thus, contrary to the view that substitutions of this type are present due to normal-cell aging, the acquisition of point mutations increases upon transformation of a normal intestinal cell into a precancerous cell.

eng
Keywords
  • APC
  • Adenomas
  • Mutational signatures
  • Organoids
  • Precancerous lesions
Citation (ISO format)
LUGLI, Natalia et al. Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue. In: Cell reports, 2017, vol. 19, n° 11, p. 2185–2192. doi: 10.1016/j.celrep.2017.05.051
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ISSN of the journal2211-1247
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