Different target genes are rate-limiting in different cancers and their susceptibility to mutations and selective advantage conferred by the mutations may vary (for example, TGFBRII and PTEN both contain coding repeats which are structurally prone to frameshift mutations in the context of deficient MMR, but TGFBRII is mainly involved in gastrointestinal cancers and PTEN in endometrial cancer [44]. The gene discussed is PTEN; the disease is cancer.