Assessment of Promoter Methylation Identifies PTCH as a Putative Tumor-suppressor Gene in Human CLL

作者：Schmidt Wolf Ingo G H^*; Plass Christoph; Byrd John C; Frevel Kathrin; Pietsch Torsten; Waha Andreas

来源：Anticancer Research, 2016, 36(9): 4515-4519.

DOI：10.21873/anticanres.10998

• Chronic lymphocytic leukemia
• methylation
• PTCH
• hedgehog pathway

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.

• 出版日期2016-9