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

• Main Authors: Natalia Lugli, Vasilis S. Dionellis, Paloma Ordóñez-Morán, Irene Kamileri, Sotirios K. Sotiriou, Joerg Huelsken, Thanos D. Halazonetis
• Format: Article
• Language: English
• Published: Elsevier 2017-06-01
• Series: Cell Reports
• Subjects: precancerous lesions; APC; adenomas; organoids; mutational signatures
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717307088

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.