Novel GPR34 and CCR6 mutation and distinct genetic profiles in MALT lymphomas of different sites
| Autor: | Alistair Robson, Joe Sneath Thompson, John R. Goodlad, Margaret Ashton-Key, Sarah Moody, Markus Raderer, Hongxiang Liu, Fangtian Wu, George S. Vassiliou, Shih-Sung Chuang, Yingwen Bi, Ming-Qing Du, Sergio Cogliatti, Iwona Wlodarska |
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| Přispěvatelé: | Vassiliou, George [0000-0003-4337-8022], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptors CCR6 Chromosomal translocation Biology medicine.disease_cause Frameshift mutation 03 medical and health sciences 0302 clinical medicine immune system diseases hemic and lymphatic diseases Exome Sequencing medicine Humans Thyroid Neoplasms Gene B cell Exome sequencing Mutation MALT lymphoma Hematology Lymphoma B-Cell Marginal Zone Genetic Profile medicine.disease Salivary Gland Neoplasms 3. Good health Lymphoma 030104 developmental biology medicine.anatomical_structure Receptors Lysophospholipid 030220 oncology & carcinogenesis Cancer research |
| Popis: | MALT lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterised. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors (GPR34 and CCR6) not previously reported in human malignancies, 3 genes (PIK3CD, TET2, TNFRSF14) not previously implicated in MALT lymphoma, and a further 2 genes (TBL1XR1, NOTCH1) recently described in MALT lymphoma. The majority of mutations in GPR34 and CCR6 were nonsense and frameshift changes clustered in the C-terminal cytoplasmic tail, and would result in truncated proteins that lack the phosphorylation motif important for β-arrestin mediated receptor desensitization and internalisation. Screening of these newly identified mutations, together with previously identified genetic changes, identified distinct mutation profiles in MALT lymphoma of various sites, with those of salivary gland characterised by frequent TBL1XR1 and GPR34 mutations, thyroid by frequent TET2, TNFRSF14 and PIK3CD mutations, and ocular adnexa by frequent TNFAIP3 mutation. Interestingly, in MALT lymphoma of the salivary gland, there was a significant positive association between TBL1XR1 mutation and GPR34 mutation/translocation (P=0.0002). In those of ocular adnexa, TBL1XR1 mutation was mutually exclusive from TNFAIP3 mutation (P=0.049), but significantly associated with IGHV3-23 usage (P=0.03) and PIK3CD mutation (P=0.009). These findings unravel novel insights into the molecular mechanisms of MALT lymphoma and provide further evidence for potential oncogenic cooperation between receptor signalling and genetic changes. ispartof: Haematologica vol:103 issue:8 pages:1329-1336 ispartof: location:Italy status: published |
| Databáze: | OpenAIRE |
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