Enhanced rate of acquisition of point mutations in mouse intestinal adenomas compared to normal tissue​. Mus musculus

The genomes of thousands of human cancers have been sequenced, revealing a large number of singlenucleotide substitutions (SNSs) per cancer. The SNSs present in cancer conform to distinct mutationsignatures, the most prevalent of which comprises C to T substitutions in the context of CpG motifs. Ithas been suggested that the SNSs belonging to this signature arise during organismal aging, beforetransformation of a normal cell to a cancer cell. However, our previous study of human colon adenomasshowed that the number of SNSs in each tumor correlates with tumor size and not patient age, arguingthat SNSs arise after cellular transformation. To resolve the two viewpoints, we sequenced organoidsderived from single intestinal normal or cancer cells of APC-mutant mice. SNSs were at least ten timesmore frequent in the tumor than in the normal cells, even though both cell types were derived from thesame mice. We propose that most mutations in intestinal cancers arise after a normal cell is transformedinto a cancer cell, contrary to the current view that mutations are acquired during organismal aging.