title: Assessment of Promoter Methylation Identifies PTCH as a Putative Tumor-suppressor Gene in Human CLL.
abstract: Chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of neoplastic lymphocytes, indicating disruption of apoptosis.
  
  
  
  Differential methylation hybridization analysis was performed to identify novel target genes silenced by CpG island methylation in patients with CLL.
  
  
  
  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.
  
  
  
  Our investigation suggests that epigenetic silencing of PTCH is a mechanism contributing to CLL tumorigenesis.
authors.affiliation: Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital, Bonn, Germany ingo.schmidt-wolf@ukb.uni-bonn.de.
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.affiliation: Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, U.S.A.
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.affiliation: Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, U.S.A.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital, Bonn, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Frevel
authors.affiliation: Department of Neuropathology, University Hospital, Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.affiliation: Department of Neuropathology, University Hospital, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D020868:Gene Silencing; D016153:Genes, Suppressor; D016147:Genes, Tumor Suppressor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D000072081:Patched-1 Receptor / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: C000606236:PTCH1 protein, human; D000072081:Patched-1 Receptor
keywords: Chronic lymphocytic leukemia; PTCH; hedgehog pathway; methylation