Fig. 4

The loss of heterozygosity of the adenomatous polyposis coli (Apc) gene was not observed through DNA sequencing. Colonic adenomas resulting from inducible loss of Apc in leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1)+/− stem cells are missing only one copy of exon 15 of the Apc gene. RNA sequencing reads from adjacent nontumor tissue (top row) and adenoma (bottom row) are plotted as pooled pileups. Allelic loss is typically considered to occur when the amount of tumor DNA was 50% or less than the value obtained from heterozygous tissue, due to the high risk of contamination from wild-type cells. Here, the sequenced tumor cells containend ~50% of the adjacent normal DNA which was assumed to be homozygous for wild-type Apc. No additional somatic mutations in Apc were observed across the nine tumors including genetic deletions, although many other Wnt/β- catenin genes were mutated