A20 deletion is associated with copy number gain at the TNFAIBIC locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands

E. Chanudet, H. Ye, J. Ferry, C. M. Bacon, P. Adam, H. K. Müller-Hermelink, J. Radford, S. A. Pileri, K. Ichimura, V. P. Collins, R. A. Hamoudi, A. G. Nicholson, A. C. Wotherspoon, P. G. Isaacson, M. Q. Du

Research output: Contribution to journalArticle

Abstract

The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array-comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2-6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array-CGH identified NF-κB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2-22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42 = 19%), salivary gland (2/24 = 8%), thyroid (1/9 = 11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFAIBIC gain were significantly associated (p <0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p = 0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p = 0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation- negative MALT lymphoma.

Original languageEnglish
Pages (from-to)420-430
Number of pages11
JournalJournal of Pathology
Volume217
Issue number3
DOIs
Publication statusPublished - Feb 2009

    Fingerprint

Keywords

  • A20
  • Array comparative genomic hybridization
  • MALT lymphoma
  • TNF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Chanudet, E., Ye, H., Ferry, J., Bacon, C. M., Adam, P., Müller-Hermelink, H. K., Radford, J., Pileri, S. A., Ichimura, K., Collins, V. P., Hamoudi, R. A., Nicholson, A. G., Wotherspoon, A. C., Isaacson, P. G., & Du, M. Q. (2009). A20 deletion is associated with copy number gain at the TNFAIBIC locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands. Journal of Pathology, 217(3), 420-430. https://doi.org/10.1002/path.2466