Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma
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
Citation and License
BMC Cancer 2012, 12:457 doi:10.1186/1471-2407-12-457Published: 5 October 2012
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.
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.
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.
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.