Epigenetic silencing of multiple genes in primary CNS lymphoma

Linda C. Chu, Charles G. Eberhart, Stuart A. Grossman, James G. Herman

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Epigenetic silencing of functionally important genes is important in the development of malignancies and is a source of potential markers for molecular detection. Primary central nervous system lymphoma (PCNSL) is an increasingly common tumor that has not been extensively examined for changes in promoter region methylation. We examined 14 tumor suppressor genes in 25 cases of PCNSL using methylation-specific PCR. Methylation was observed in DAPK (84%), TSP1 (68%), CRBP1 (67%), p16INK4a (64%), p14ARF (59%), MGMT (52%), RARβ2 (50%), TIMP3 (44%), TIMP2 (42%), p15INK4b (40%), p73 (28%), hMLH1 (12%), RB1 (8%) and GSTP1 (8%). Promoter methylation of p14ARF, p16INK4a and MGMT was correlated with loss of expression by immunohistochemical staining. The methylation of many of these genes in PCNSL is similar to that reported in other high-grade B-cell lymphomas. All 25 cases of PCNSL had methylation of at least 2 genes. Methylation of DAPK, p16INK4a or MGMT was found in 96% of the tumors, suggesting simple marker strategies to detect circulating methylated DNA in serum that might facilitate early tumor detection. Our study provides insight into the epigenetic alterations in PCNSL and provides potential biomarkers of disease.

Original languageEnglish (US)
Pages (from-to)2487-2491
Number of pages5
JournalInternational Journal of Cancer
Issue number10
StatePublished - Nov 15 2006


  • DNA methylation
  • Primary CNS lymphoma
  • Tumor suppressor genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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