Fig. 5

Kidney PT shows a unique somatic mutation pattern that confers high risk for tumor transformation. a Epidemiologic data showing the percentage of kidney tumors either derived from the proximal tubule, such as KIRC (clear cell renal cell carcinoma) and KIRP (papillary cell renal cell carcinoma), or from other kidney structures (other subtypes). b Somatic mutation burden in KT1, KT2, KIRP, and KIRC of either a younger (30–40) or older (60–70) age range. Significance among older groups was measured by one-way ANOVA. c, d Linear fit with age (c) and yearly increase (d) of potentially pathogenic variants in KT2 vs KT1-SAT-VAT clones. Potentially pathogenic variants are defined as follows: all variants were annotated with CADD (Combined Annotation Dependent Depletion; https://cadd.gs.washington.edu/). SNVs and InDels predicted to affect the coding sequence (presenting CADD score > 15) were selected and subsequently filtered on expression data in order to select only variants affecting a gene actually expressed in the tissue of origin of the clone. Tissue-specific and non-tissue-specific genes correspond to the expressed and non-expressed genes in the corresponding tissue according to the Human Protein Atlas (http://proteinatlas.com). Adjusted P values of the linear fit are calculated with the linear mixed model (c) or two-sided t test (d). e Enrichment (upward bars) or depletion (downward bars) of somatic mutations in indicated genomic features. The log2 ratio of the number of observed and expected point mutations indicates the effect size of the enrichment or depletion in each region. Log2 = 0 corresponds to a number of observed mutations equal to the number expected by random distribution. f Enrichment (upward bars) or depletion (downward bars) of somatic mutations in conserved and non-conserved regions of the genome. ^#P < 0.05, one-sided binomial test. ***P < 0.001, ****P < 0.0001 two-sided t test of log2 ratios for either KT2 or KT1-SAT-VAT in specified genomic regions. EP epidermis, KT1 kidney tubule 1, KT2 kidney tubule 2, SAT subcutaneous fat, VAT visceral fat