title: 20q11.1 amplification in giant-cell tumor of bone: Array CGH, FISH, and association with outcome.
abstract: The goal of this study was to identify recurrent regions of genomic gain or loss in giant-cell tumor of bone (GCTb). Array comparative genomic hybridization (aCGH) was performed for 20 frozen tumor samples of GCTb. A separate subset of 59 GCTb with outcome data was used for validation. The most frequent region of change identified by aCGH was gain of a 1-Mbp region at 20q11.1. In the validation arm of 59 cases the minimal common region of copy number gain at 20q11.1, seen in 54% of the samples, was BAC clone RP11-4O9, which contained the genes TPX2 and BCL2L1. For most cases, amplification was restricted to the mononuclear component and was not present in the multinucleated giant cells. Southern blot for TPX2 and BCL2L1 identified the former as the gene with the highest level of amplification for these two proposed candidate genes of importance. Immunohistochemistry for TPX2 expression correlated with amplification, while BCL2L1 expression was not identified. Kaplan-Meier curves for progression-free survival showed a statistically significant difference for cases with 20q11.1 amplification (P = 0.0001). Univariate analysis involving Cox proportional hazards models did not show a significant difference for initial treatment type (curettage versus resection) (P = 0.575), age (</=50 vs. >50) (P = 0.543), or sex (P = 0.268), but did correlate with 20q11.1 amplification (P = 0.001). By multivariate analysis, it was found that 20q11.1 amplification (P = 0.001) was the only factor to reach statistical significance. 20q11.1 amplification can be used as a marker of prognostic importance in GCTb. We propose TPX2 as a candidate oncogene in the core-amplified region at 20q11.1.
authors.affiliation: Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Arthur James Cancer Hospital and Richard Solove Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Smith
authors.forename: Joel
authors.initials: J
authors.lastname: Mayerson
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: David
authors.initials: D
authors.lastname: Suster
authors.forename: Nehad
authors.initials: N
authors.lastname: Mohammed
authors.forename: Susan
authors.initials: S
authors.lastname: Long
authors.forename: Herbert
authors.initials: H
authors.lastname: Auer
authors.forename: Susie
authors.initials: S
authors.lastname: Jones
authors.forename: Christina
authors.initials: C
authors.lastname: McKeegan
authors.forename: Gregory
authors.initials: G
authors.lastname: Young
authors.forename: Gary
authors.initials: G
authors.lastname: Bos
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D002890:Chromosomes, Human, Pair 20; D005260:Female; D005784:Gene Amplification; D005870:Giant Cell Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C494811:BCL2L1 protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C122167:TPX2 protein, human; D051020:bcl-X Protein