title: Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle-cell lymphomas.
abstract: OBJECTIVE
  Mantle cell lymphoma (MCL), a mature B-cell neoplasm, is genetically characterized by the translocation t(11;14)(q13;q32). However, secondary alterations are required for malignant transformation. The identification of inactivated tumor suppressor genes contributing to the development of MCL may lead to further elucidation of the biology of this disease and help to identify novel targets for therapy.
  
  
  METHODS
  Whole genome microarray-based gene expression profiling on treated versus untreated MCL cell lines was used to identify genes induced by 5-aza-2'-deoxycytidine. The degree of promoter methylation and transcriptional silencing of selected genes was then proven in MCL cell lines and primary cases by methylation-specific polymerase chain reaction (PCR) techniques, real-time PCR and gene expression profiling.
  
  
  RESULTS
  After 5-aza-2'-deoxycytidine treatment, we identified more than 1000 upregulated genes, 16 of which were upregulated > or =3-fold. Most of them were not known to be silenced by methylation in MCL. A low expression of ING1, RUNX3 and BNIP3L was observed in three of the five the MCL cell lines. In addition, the expression of PARG1, which is located in the frequently deleted region 1p22.1, was substantially reduced and displayed at least partial promoter methylation in all investigated MCL cell lines as well as in 31 primary MCL cases.
  
  
  CONCLUSIONS
  In summary, we identified interesting novel candidate genes that probably contribute to the progression of MCL and suggest that PARG1 is a strong candidate tumor suppressor gene in MCL.
authors.affiliation: Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Ripperger
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kamphues
authors.forename: Makito
authors.initials: M
authors.lastname: Emura
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.forename: Marcel
authors.initials: M
authors.lastname: Tauscher
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
authors.forename: Patricia
authors.initials: P
authors.lastname: Groenen
authors.forename: Britta
authors.initials: B
authors.lastname: Skawran
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rudolph
authors.forename: Evelyne
authors.initials: E
authors.lastname: Callet-Bauchu
authors.forename: Johan H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics; D000077209:Decitabine; D018450:Disease Progression; D020690:GTPase-Activating Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic
chemical_list: C500429:ARHGAP29 protein, human; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; D000077209:Decitabine; D001374:Azacitidine