Assessment of promoter methylation identifies ptch as a putative tumor-suppressor gene in human cll

Abstract

Background: Chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of neoplastic lymphocytes, indicating disruption of apoptosis. Patients and Methods: Differential methylation hybridization analysis was performed to identify novel target genes silenced by CpG island methylation in patients with CLL. Results: Patched (PTCH), a tumor-suppressor gene, was found to be frequently methylated in CLL samples compared to samples derived from healthy individuals. De novo methylation of a CpG island region located upstream of PTCH exon 1 was confirmed by pyrosequencing in 17/37 (46%) of peripheral blood mononuclear cells of patients with CLL, but in none isolated from seven healthy individuals. No association was found between PTCH hypermethylation and currently used prognostic CLL factors. Conclusion: Our investigation suggests that epigenetic silencing of PTCH is a mechanism contributing to CLL tumorigenesis.