Fig. 2

Genetic and clinical characteristics of MSI-H individuals. a CoMut plot displaying germline, somatic, and epigenetic events in L-MMR genes (bottom 4 rows—number of affected individuals in parentheses) for 217 MSI-H individuals (columns). The top histogram represents MSI burden expressed as the fraction of possible microsatellite sites that are unstable. Age of diagnosis was converted to a Z-score using the mean and standard deviation age for each cancer type. Cancer types with fewer than 5 MSI-H individuals are labeled “Other” and include bladder, head and neck, kidney, glioma, lung, liver, prostate, stomach, and rectal cancer. The type of genetic alteration is indicated by color, and bi-allelic events are indicated by a black box. Individuals with bi-allelic (germline:somatic) MMR mutations are grouped to the left. The red arrow highlights an individual with bi-allelic alteration in MSH5 (not an L-MMR gene). b Somatic MSI burden in 4997 TCGA individuals grouped by type of MMR pathway alteration. Categories are the same as those described in Fig. 1: Bi-allelic, combined germline and somatic alteration of the same gene; Mixed, germline and somatic alteration of different genes in the set; Germ, germline alterations only; and Som, somatic alterations only (mutation or methylation). Individuals with bi-allelic alteration occurring via germline:somatic and germline:methylation mechanisms are displayed separately. The number of individuals in each category is indicated in parentheses