PubMed:28479318 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/28479318","sourcedb":"PubMed","sourceid":"28479318","text":"Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing.\nTo determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma subtypes, we analyzed a total cohort of 20 PCLBCL-LT patients by using next-generation sequencing with a lymphoma panel designed for diffuse large B-cell lymphoma. We also analyzed 12 pairs of tumor and control DNA samples by whole-exome sequencing, which led us to perform resequencing of three selected genes not included in the lymphoma panel: TBL1XR1, KLHL6, and IKZF3. Our study clearly identifies an original mutational landscape of PCLBCL-LT with a very restricted set of highly recurrent mutations (\u003e40%) involving MYD88 (p.L265P variant), PIM1, and CD79B. Other genes involved in B-cell signaling, NF-κB activation, or DNA modeling were found altered, notably TBL1XR1 (33%), MYC (26%) CREBBP (26%), and IRF4 (21%) or HIST1H1E (41%). MYD88(L265P) variant was associated with copy number variations or copy neutral loss of heterozygosity in 60% of patients. The most frequent genetic losses involved CDKN2A/2B, TNFAIP3/A20, PRDM1, TCF3, and CIITA. Together, these results show that PCLBCL-LT exhibits a unique mutational landscape, combining highly recurrent hotspot mutations in genes involved in NF-kB and B-cell signaling pathways, which provides a rationale for using selective inhibitors of the B-cell receptor.","tracks":[{"project":"PubTator4TogoVar","denotations":[{"id":"28479318_0","span":{"begin":841,"end":848},"obj":"ProteinMutation"}],"attributes":[{"id":"28479318_0_ProteinMutation","pred":"proteinmutation","subj":"28479318_0","obj":"rs387907272"},{"subj":"28479318_0","pred":"source","obj":"PubTator4TogoVar"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubTator4TogoVar","color":"#ece493","default":true}]}]}}