title: A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma.
abstract: Combined deletion of chromosomes 1p and 19q is associated with improved prognosis and responsiveness to therapy in patients with anaplastic oligodendroglioma. The deletions usually involve whole chromosome arms, suggesting a t(1;19)(q10;p10). Using stem cell medium, we cultured a few tumors. Paraffin-embedded tissue was obtained from 21 Mayo Clinic patients and 98 patients enrolled in 2 North Central Cancer Treatment Group (NCCTG) low-grade glioma trials. Interphase fusion of CEP1 and 19p12 probes detected the t(1;19). 1p/19q deletions were evaluated by fluorescence in situ hybridization. Upon culture, one oligodendroglioma contained an unbalanced 45,XX,t(1;19)(q10;p10). CEP1/19p12 fusion was observed in all metaphases and 74% of interphase nuclei. Among Mayo Clinic oligodendrogliomas, the prevalence of fusion was 81%. Among NCCTG patients, CEP1/19p12 fusion prevalence was 55%, 47%, and 0% among the oligodendrogliomas, mixed oligoastrocytomas, and astrocytomas, respectively. Ninety-one percent of NCCTG gliomas with 1p/19q deletion and 12% without 1p/19q deletion had CEP1/19p12 fusion (P < 0.001, chi(2) test). The median overall survival (OS) for all patients was 8.1 years without fusion and 11.9 years with fusion (P = 0.003). The median OS for patients with low-grade oligodendroglioma was 9.1 years without fusion and 13.0 years with fusion (P = 0.01). Similar significant median OS differences were observed for patients with combined 1p/19q deletions. The absence of alterations was associated with a significantly shorter OS for patients who received higher doses of radiotherapy. Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined 1p/19q deletion in human gliomas. Like combined 1p/19q deletion, the 1;19 translocation is associated with superior OS and progression-free survival in low-grade glioma patients.
authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA. rjenkins@mayo.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Hilary
authors.initials: H
authors.lastname: Blair
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Robert M
authors.initials: RM
authors.lastname: Arusell
authors.forename: Mark
authors.initials: M
authors.lastname: Law
authors.forename: Heather
authors.initials: H
authors.lastname: Flynn
authors.forename: Sandra
authors.initials: S
authors.lastname: Passe
authors.forename: Sara
authors.initials: S
authors.lastname: Felten
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D007399:Interphase; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D011379:Prognosis; D014178:Translocation, Genetic
chemical_list: C474898:CNTRL protein, human; D018797:Cell Cycle Proteins