Recurrent CDKN1B mutations in classical HCL. (A) Cancer consensus and COSMIC annotated gene mutations identified in HCL by whole exome sequencing. Patient 3 progressed after vemurafenib treatment and was sequenced before and after BRAFi (vemurafenib) treatment. Exome sequencing identified recurrent inactivating somatic mutations of CDKN1B (for complete list of somatic mutations see supplemental Table 1b). (B) Gene regions of CDKN1B and distribution of mutations in HCL. Binding regions of important interaction partners are shown below the gene diagram. There were 17 CDKN1B mutations identified in 13 patients. In cases in which normal material was not available for the remaining mutations with sufficient read coverage (mean = 1259 reads, supplemental Table 1) the allele frequencies indicated somatic origin (supplemental Figure 2). (C) Frequency of CDKN1B mutations across cancer entities. Mutation frequencies were obtained from http://www.cbioportal.org/public-portal/.15 HCL shows the highest CDKN1B mutations frequency in cancer. ACyC, adenoid cystic carcinoma; CCLE, Cancer Cell Line Encyclopedia; ccRCC, clear cell renal cell carcinoma; GBM, glioblastoma multiforme; MM, Multiple myelomach; pRCC, papillary renal cell carcinoma; RCC, chromophobe renal cell carcinoma.
