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

Anticancer Res. 2016 Sep;36(9):4515-9. doi: 10.21873/anticanres.10998.


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.

Keywords: Chronic lymphocytic leukemia; PTCH; hedgehog pathway; methylation.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Exons
  • Female
  • Gene Silencing
  • Genes, Suppressor
  • Genes, Tumor Suppressor*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukocytes, Mononuclear / cytology
  • Male
  • Middle Aged
  • Patched-1 Receptor / genetics*
  • Patched-1 Receptor / metabolism*
  • Promoter Regions, Genetic*
  • Sequence Analysis, DNA


  • PTCH1 protein, human
  • Patched-1 Receptor