Extended Data Fig. 8: Mutation frequencies in the different T-cell populations at the time point of lymphoma development.

All nonsynonymous somatic single nucleotide variants and indels that passed quality control (see Methods) were included. The filled colors of the bar plot segments represent genomic locations of retained variants for tumor mutational burden (TMB) analysis. TMB was calculated per hg38 effective genome size (3,049 mb; Hg38 7-way Genome size statistics - genomewiki). We detected a higher TMB in the CAR+CD5- (1.9 Mut/Mb) and the CAR+CD5+ (0.8 Mut/Mb) populations compared to the CAR-CD5+ (0.1 Mut/Mb) population. These results showed that TMB in the neoplastic CAR+ clones were within the range of a recently published (Schrader et al Nat Commun 2018) whole exome sequencing (WES, NimbleGen SeqCap EZ Exome v3: 64,000,000 bp) cohort of 17 T-cell prolymphocytic leukemia (T-PLL) patients (median TMB: 1.1 Mut/Mb; range, 0.2 – 2.3) and 2 T-cell large granular lymphocyte (LGL) patients (median TMB: 1.1 Mut/Mb). WGS TMB was consistent after filtering mutations in coding DNA sequences (CDS) and untranslated regions (UTR) of protein-coding genes divided by genome size of the respective regions (84 Mb) in hg38 build using the GENCODE v46 annotations (CAR+CD5-: 2.0 Mut/Mb, CAR+CD5+: 0.7 Mut/Mb; CAR-CD5+: 0.1 Mut/Mb).