Lugli, NataliaDionellis, Vasilis S.Ordonez-Moran, PalomaKamileri, IreneSotiriou, Sotirios K.Huelsken, JoergHalazonetis, Thanos D.2017-09-052017-09-052017-09-05201710.1016/j.celrep.2017.05.051https://infoscience.epfl.ch/handle/20.500.14299/140304WOS:000403207700002The 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 Apc(min/+) 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.text::journal::journal article::research article