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Open Access Research article

Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma

Junko Nomoto12, Nobuhiro Hiramoto1, Motohiro Kato3, Masashi Sanada3, Akiko Miyagi Maeshima4, Hirokazu Taniguchi4, Fumie Hosoda5, Yoshitaka Asakura1, Wataru Munakata1, Naohiro Sekiguchi1, Dai Maruyama1, Takashi Watanabe1, Hitoshi Nakagama6, Kengo Takeuchi7, Kensei Tobinai1, Seishi Ogawa3 and Yukio Kobayashi1*

Author Affiliations

1 Hematology Division, National Cancer Center Hospital, Tokyo, Japan

2 Section of Microbiology and Immunology, Tokyo Medical and Dental University Graduate School of Health Care Sciences, Tokyo, Japan

3 Cancer Genomics, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

4 Pathology Division, National Cancer Center Hospital, Tokyo, Japan

5 Cancer Genomics Division, National Cancer Center Research Institute, Tokyo, Japan

6 Early Carcinogenetic Division, Research Institute, National Cancer Center Hospital, Tokyo, Japan

7 Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

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BMC Cancer 2012, 12:457  doi:10.1186/1471-2407-12-457

Published: 5 October 2012

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.

Keywords:
FICTION analysis; Hodgkin lymphoma; TNFAIP3 gene; Homozygous deletion