title: MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome.
abstract: OBJECTIVE
  To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion.
  
  
  METHODS
  Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation.
  
  
  RESULTS
  Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance.
  
  
  CONCLUSIONS
  MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.
authors.affiliation: Division of Orthopedic Oncology, Department of Pathology, Center for Biostatistics, The Arthur James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Medical School, Columbus, OH, USA. morrison-4@medctr.osu.edu
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Michael
authors.initials: M
authors.lastname: Radmacher
authors.forename: Nehad
authors.initials: N
authors.lastname: Mohammed
authors.forename: David
authors.initials: D
authors.lastname: Suster
authors.forename: Herbert
authors.initials: H
authors.lastname: Auer
authors.forename: Susie
authors.initials: S
authors.lastname: Jones
authors.forename: Judy
authors.initials: J
authors.lastname: Riggenbach
authors.forename: Nicole
authors.initials: N
authors.lastname: Kelbick
authors.forename: Gary
authors.initials: G
authors.lastname: Bos
authors.forename: Joel
authors.initials: J
authors.lastname: Mayerson
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology; D002898:Chromosomes, Human, Pair 8; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc