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Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M et al.. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66: 9852-9861

Wake Forest University, Winston-Salem, North Carolina, United States
Cancer Research (Impact Factor: 9.28). 11/2006; 66(20):9852-61. DOI: 10.1158/0008-5472.CAN-06-1796
Source: PubMed

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.

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    • "Grade II and grade III oligodendrogliomas are equally affected by these chromosomal lesions, suggesting an early role in oligodendroglial tumorigenesis. Since losses of chromosome 1p and 19q are intimately correlated (Jenkins et al., 2006), it is plausible that the corresponding putative tumor suppressor genes may be involved in biologically distinct pathways, which may act synergistically in oligodendroglial tumorigenesis. Allelic losses of chromosomes 9p and 10q, and homozygous deletion of CDKN2A on chromosome 9p21, are also frequent in anaplastic oligodendroglioma (WHO grade III) (Bigner et al., 1999; Ueki et al., 2002). "
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    • "Glioblastomas are typically associated with epidermal growth factor receptor (EGFR) amplification (usually associated with chromosome 10 loss and gain of chromosome 7); and oligodendroglial tumors are often associated with deletion of chromosome 1p and 19q. These two molecular features are mutually exclusive [48] [49]. Using microarray analysis, Ducray et al. reported that AKR1C3 is among a set of 22 genes that can distinguish gliomas with EGFR amplification and oligodendroglimas with 1p19q codeletion [50]. "
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