Figure 1: The mutational spectrum of TSC1 and TSC2 in TSC patient samples.

(a) SNVs and INDELs in TSC2 and TSC1 (each mutation shown only once per patient). (b) Large TSC2 deletion in 10-RA1 identified by SNP array. Black dots: log-R ratios (LRR) of probe intensities; lower panel: magnification of boxed region. (c) Intragenic TSC2 deletion in 63-UG1 identified by targeted sequencing; grey bars: read counts along TSC2; blue bars: exons. (d) Blue bars: large deletions in TSC2. X-axis is broken to accommodate 32-SEGA1 deletion. (e,f) Example CN-LOH events as involving TSC1 on chromosome 9q in 38-SEGA1 (e) and TSC2 on chromosome 16p in 27-SEGA1 (f). (g) Percentage of 66 TSC patients with a mutation in TSC1, TSC2 or neither (NMI). (h) Percentage of tumours with 1 or 2 TSC1/TSC2 mutations identified. (i) Percentage of TSC1/TSC2 mutant tumours with 2 hits. Only 1-hit lesions with all 3 DNA platforms completed included (Supplementary Data 2). (j) Percentage of germline and somatic TSC1/TSC2 mutations of each type. (k) Total number of TSC1/TSC2 mutations of each class for each lesion type. (l) Combinations of mutations in TSC1 and TSC2 mutant tumours. (m,n) Relative TSC2 (m) and TSC1 (n) mRNA expression in non-TSC tissues (n=11) and TSC lesions grouped by mutational status (TSC2 mutation: 1 (n=11) or 2 (n=14); TSC1 mutation: 1 (n=2) or 2 (n=3)). FDR-adjusted P values from individual Welch’s t-tests: **P<0.01; *P<0.05). Open circles represent individual tumours and bars represent mean and s.d. CN-LOH, copy-neutral loss-of-heterozygosity; CPM, counts per million; DEL, deletion; FS, frameshift; IFD, in-frame deletion; MS, missense; Mut, mutation; NMI, no mutation identified; NS, nonsense; SPL, splicing.