Fig. 6
Dysregulated TCL1 and lesions in ATM as the genetic basis of T-PLL. a Genetic events across all analyzed T-PLL cases (one circle per gene). y-axis: sCNA-affected (CN-mean over all T-PLL, 83 cases); x-axis: mutated (mean VAF over all detected mutations, 54 cases); circle size: mutation frequency among all cases; circle border coloring: FDR < 0.1 of mutations; circle color: fc-gene expression (70 cases). Somatic mutations (SNVs and small indels) with at least one damaging prediction were considered. Selection criteria for visualized genes: CN-affected (CN > 2.2; CN < 1.8) and mutated at significant (FDR < 0.1) and/or at prominent clonal (VAF > 0.5; see Fig. 4d) level. ATM was the most prominent gene affected by CN losses and mutations of high VAFs, associated with overall mRNA downregulation. b Presence of dominant lesions detected in GEP (high/low expression), sCNA (gain/loss), and mutation (present/absent) profiling summarized for 84 T-PLL (red: lesion present, blue: lesion absent, gray: not analyzed). Chromosomal complexity: moderate with <2000 (n = 25) and high with >5000 (n = 26) sCNA-affected genes. Order of cases according to the number of calls in the following 8 ‘lesional categories’: (1) overall TCL1 / MTCP1 affected (note that there were no mutations detected in TCL1 genes), (2) overall ATM affected, (3) AGO2 sCNA present, (4) AGO1/AGO3/AGO4 UPD present, (5) MYC sCNA present or MYC mRNA upregulated, (6) IL2RG/JAK1/JAK3/STAT5B mutated, and differentially expressed genes associated with epigenetic regulators (7; Supplementary Data 20) or DDR (8; Supplementary Data 21). Each case was affected by at least one of these core lesions
