Frequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma

Li Fu, Zifen Gao, Xiaohua Zhang, Ying Hung Tsang, Hwee Koon Goh, Hua Geng, Norio Shimizu, Junjiro Tsuchiyama, Gopesh Srivastava, Qian Tao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Nasal NK/T-cell lymphoma (NL) is a rare but clinically important entity of lymphoma. Its preferential incidence in Orientals but not Caucasians suggests possible genetic predisposition. 11q deletion is common in NL, indicating certain tumor suppressor genes (TSGs) at this locus involved in its pathogenesis. We investigated the expression and methylation of an 11q23.2 TSG, CADM1 (or TSLC1), and its partner DAL-1 (or EPB41L3) in NL. Methylation and silencing of CADM1 were detected in 2 NL and 4 of 8 (50%) of non-Hodgkin lymphoma (NHL) cell lines, but not in normal NK cells and normal PBMC. Absence of CADM1 protein was also detected in NL cell lines. 5-aza-20 -deoxycytidine (Aza) demethylation or genetic knockout of both DNMT1 and 3B genes restored CADM1 and DAL-1 expression. CADM1 methylation was further detected in 36 of 45 (80%) of NL tumors. Concomitantly, DAL-1 was epigenetically inactivated in NL cell lines and virtually all the tumors with methylated CADM1. A significant correlation between the methylation of both genes was found (p < 0.0001). Homozygous deletion of CADM1 was detected in only 3 of 18 (17%) of tumors. The stress-response of CADM1 was abolished when its promoter becomes methylated. Our results demonstrate a frequent, predominant epigenetic silencing of CADM1 and DAL- 1 in NL, which likely play a synergic role in NL pathogenesis.

Original languageEnglish (US)
Pages (from-to)1572-1578
Number of pages7
JournalInternational Journal of Cancer
Volume124
Issue number7
DOIs
StatePublished - Apr 1 2009

Keywords

  • CADM1
  • DAL-1
  • Methylation
  • Nasal lymphoma
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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