Ingo G H Schmidt-Wolf1, Christoph Plass2, John C Byrd2, Kathrin Frevel3, Torsten Pietsch4, Andreas Waha4. 1. Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital, Bonn, Germany ingo.schmidt-wolf@ukb.uni-bonn.de. 2. Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, U.S.A. 3. Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital, Bonn, Germany. 4. Department of Neuropathology, University Hospital, Bonn, Germany.
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. Copyright
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. Copyright