Fig. 1: Genetic events and their timing in HPV– HNSCC.
From: Inferring early genetic progression in cancers with unobtainable premalignant disease
a, Diagram of HPV– genetic progression determined by Califano et al.8 from tissue samples taken near the tissue surface at different stages of disease progression with associated genetic events (left to right). b, Conceptual basis of estimating timing within tumors. The loss of chromosome arm 17p most likely occurred before the WGD event. The mutation TP53R248Q most likely occurred before WGD, based on estimated multiplicity. Additional mutations (purple) are used to estimate the mutational relative timing of the WGD event. c,d, Examples of timing of genetic events in individual tumor samples; –, chromosome arm loss; +, chromosome arm gain; –/–, homozygous deletion in the indicated gene. e, CoMut plots for 421 HPV– HNSCCs. For each tumor, from top to bottom, the number of mutations, their mutational signatures, MATH, FGA, the presence of whole-genome amplification (WGD and WGT), smoking within 15 years of diagnosis and selected genetic events are shown. The shading corresponds to timing of individual events. MSI, microsatellite instability. f, Relative timing of genetic events based on 421 HPV– HNSCCs. The analysis compared 43 events among tumors: whole-genome amplification (WGD and WGT), arm losses examined by Califano et al.8 (names are colored with respect to timing groups in a) and other events with notable prevalence among HPV– tumors (Methods). Events are ordered top to bottom by the point estimates of their mRT scores. Violin plots illustrate the posterior distributions of relative timing. The event prevalence and type (color coded) are displayed to the right of the corresponding violin plot.
