1. Deletion of the TNFAIP3/A20gene detected by FICTION analysis in classical Hodgkin lymphoma
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Seishi Ogawa, Wataru Munakata, Kengo Takeuchi, Takashi Watanabe, Motohiro Kato, Akiko Miyagi Maeshima, Masashi Sanada, Kensei Tobinai, Yoshitaka Asakura, Hirokazu Taniguchi, Dai Maruyama, Fumie Hosoda, Hitoshi Nakagama, Naohiro Sekiguchi, Nobuhiro Hiramoto, Yukio Kobayashi, and Junko Nomoto
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Adult ,Male ,Cancer Research ,CD30 ,Adolescent ,Genotype ,Fluorescent Antibody Technique ,Ki-1 Antigen ,Biology ,Immunofluorescence ,lcsh:RC254-282 ,TNFAIP3 ,Young Adult ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Genetics ,Homozygous deletion ,Humans ,skin and connective tissue diseases ,Gene ,In Situ Hybridization, Fluorescence ,Tumor Necrosis Factor alpha-Induced Protein 3 ,Aged ,TNFAIP3 gene ,Aged, 80 and over ,Analysis of Variance ,medicine.diagnostic_test ,Intracellular Signaling Peptides and Proteins ,Nuclear Proteins ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,Hodgkin Disease ,DNA-Binding Proteins ,Oncology ,Mutation testing ,TNFAIP3 Gene ,Female ,Stem cell ,FICTION analysis ,Hodgkin lymphoma ,Gene Deletion ,Research Article - Abstract
Background The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-κB signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies. However, the detection of this in primary Hodgkin lymphoma (HL) specimens is hampered by the scarcity of Hodgkin Reed-Sternberg (HR-S) cells even after enrichment by micro-dissection. Methods We used anti-CD30 immunofluorescence with fluorescence in-situ hybridization (FISH) to evaluate the relative number of TNFAIP3/CEP6 double-positive signals in CD30-positive cells. Results From a total of 47 primary classical Hodgkin lymphoma (cHL) specimens, 44 were evaluable. We found that the relative numbers of TNFAIP3/CD30 cells were distributed among three groups, corresponding to those having homozygous (11%), heterozygous (32%), and no (57%) deletions in TNFAIP3. This shows that TNFAIP3 deletions could be sensitively detected using our chosen methods. Conclusions Comparing the results with mutation analysis, TNFAIP3 inactivation was shown to have escaped detection in many samples with homozygous deletions. This suggests that TNFAIP3 inactivation in primary cHL specimens might be more frequent than previously reported.
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