Deletion of the TNFAIP3/A20gene detected by FICTION analysis in classical Hodgkin lymphoma

BMC Cancer

Research Article

Fumie Hosoda¹  Seishi Ogawa²  Motohiro Kato²  Masashi Sanada²  Hitoshi Nakagama³  Kensei Tobinai⁴  Wataru Munakata⁴  Dai Maruyama⁴  Nobuhiro Hiramoto⁴  Takashi Watanabe⁴  Yoshitaka Asakura⁴  Yukio Kobayashi⁴  Naohiro Sekiguchi⁴  Junko Nomoto⁵  Akiko Miyagi Maeshima⁶  Hirokazu Taniguchi⁶  Kengo Takeuchi⁷ 

[1] Cancer Genomics Division, National Cancer Center Research Institute, Tokyo, Japan;Cancer Genomics, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;Early Carcinogenetic Division, Research Institute, National Cancer Center Hospital, Tokyo, Japan;Hematology Division, National Cancer Center Hospital, Tokyo, Japan;Hematology Division, National Cancer Center Hospital, Tokyo, Japan;Section of Microbiology and Immunology, Tokyo Medical and Dental University Graduate School of Health Care Sciences, Tokyo, Japan;Pathology Division, National Cancer Center Hospital, Tokyo, Japan;Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan;

关键词: FICTION analysis;    Hodgkin lymphoma;    TNFAIP3;    Homozygous deletion;   

DOI  :  10.1186/1471-2407-12-457

 received in 2012-05-30, accepted in 2012-10-02,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsWe 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.ResultsFrom 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.ConclusionsComparing 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.

【 授权许可】

Unknown   
© Nomoto et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.