title: Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival.
abstract: OBJECTIVE
  Regions on 1p with recurrent deletions in presenting myeloma patients were examined with the purpose of defining the deletions and assessing their survival impact.
  
  
  METHODS
  Gene mapping, gene expression, FISH, and mutation analyses were conducted on patient samples from the MRC Myeloma IX trial and correlated with clinical outcome data.
  
  
  RESULTS
  1p32.3 was deleted in 11% of cases, and deletion was strongly associated with impaired overall survival (OS) in patients treated with autologous stem cell transplant (ASCT). In patients treated less intensively, del(1)(p32.3) was not associated with adverse progression-free survival (PFS) or OS. The target of homozygous deletions was CDKN2C, however its role in the adverse outcome of cases with hemizygous deletion was less certain. 1p22.1-21.2 was the most frequently deleted region and contained the candidate genes MTF2 and TMED5. No mutations were identified in these genes. 1p12 was deleted in 19% of cases, and deletion was associated with impaired OS in univariate analysis. The target of homozygous deletion was FAM46C, which was mutated in 3.4% of cases. When cases with FAM46C deletion or mutation were considered together, they were strongly associated with impaired OS in the intensive treatment setting.
  
  
  CONCLUSIONS
  Deletion of 1p32.3 and 1p12 was associated with impaired OS in myeloma patients receiving ASCT. FAM46C was identified as a gene with potential pathogenic and prognostic significance based on the occurrence of recurrent homozygous deletions and mutations.
authors: The Institute of Cancer Research, Haemato-oncology Research Unit, Division of Molecular Pathology, London, United Kingdom.
authors: Kevin D
authors: KD
authors: Boyd
authors: Fiona M
authors: FM
authors: Ross
authors: Brian A
authors: BA
authors: Walker
authors: Christopher P
authors: CP
authors: Wardell
authors: William J
authors: WJ
authors: Tapper
authors: Laura
authors: L
authors: Chiecchio
authors: Gianpaolo
authors: G
authors: Dagrada
authors: Zoe J
authors: ZJ
authors: Konn
authors: Walter M
authors: WM
authors: Gregory
authors: Graham H
authors: GH
authors: Jackson
authors: J Anthony
authors: JA
authors: Child
authors: Faith E
authors: FE
authors: Davies
authors: Gareth J
authors: GJ
authors: Morgan
mesh_terms: D000368:Aged; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics*; D015999:Multivariate Analysis; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D063151:Polycomb Repressive Complex 2; D016016:Proportional Hazards Models; D014157:Transcription Factors / Q000235:genetics
chemical_list: C493971:CDKN2C protein, human; D050763:Cyclin-Dependent Kinase Inhibitor p18; C570567:MTF2 protein, human; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2