Assessment of Promoter Methylation Identifies PTCH as a Putative Tumor-suppressor Gene in Human CLL.
Schmidt-Wolf IG, Plass C, Byrd JC, Frevel K, Pietsch T, Waha A
Anticancer Res 36 4515-9 01/01/2016
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.