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

ArticleinCancer Research 66(20):9852-61 · November 2006with28 Reads
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.
    • "mixed, mixed oligoastrocytic histology; CFO, classic for oligodendroglial morphology. and the latter one being subsequently deleted during gliomagenesis [13, 18], 1p/19q codeletion was one of the most representative and remarkable molecular markers in diffuse gliomas with diagnostic, prognostic and predictive utilities in clinical practice [7, 19]. The marker served as a stratifier in clinical trials and was shown to predict therapeutic response to PCV chemotherapy (procarbazine, lomustine and vincristine) and radiotherapy in oligodendroglial tumors [1, 5]. "
    Full-text · Article · Nov 2014
    • "A minor fraction of GBMs (0.8%, 2/240) contained mutations in both the TERT promoter and IDH1/2 suggesting they were treated oligodendrogliomas that were diagnosed as small cell GBMs. Loss of chromosomal arms 1p and 19q is a wellknown genetic event associated with oligodendrogliomas that many neuropathologists use as a reliable test for diagnosing oligodendroglioma, a tumor generally associated with favorable prognosis and response to chemotherapy29303132. As a secondary analysis, the 69 oligodendrogliomas with 1p/19q status available were analyzed for an association with TERT promoter/IDH1/2 mutational status. "
    [Show abstract] [Hide abstract] ABSTRACT: Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.
    Full-text · Article · Jan 2014
    • "Pediatric gliomagenesis seems to follow different molecular pathways from adults. Concurrent deletion of 1p and 19q is the hallmark of adult oligodendrogliomas (identified in up to 80% of tumors) [16-18] and results from an unbalanced t (1;19) (q10; p10) [19,20]. Assessment of allelic status at 1p and 19q has been established as a key tool for the diagnosis, treatment and prognosis of adult oligodendrogliomas, given that tumors carrying the co-deletion usually have a more favorable response to conventional chemotherapy agents [21,22]. "
    [Show abstract] [Hide abstract] ABSTRACT: Pediatric oligodendrogliomas are rare and appear to show a different molecular profile from adult tumors. Some gliomas display allelic losses at 1p/19q in pediatric patients, although less frequently than in adult patients, but this is rare in tumors with an oligodendroglial component. The molecular basis of this genomic abnormality is unknown in pediatric gliomas, but it represents a relatively common finding in pediatric oligodendroglioma-like neoplasms with leptomeningeal dissemination. Multiplex ligation-dependent probe amplification (MLPA) analysis using SALSA P088-B1 for the analysis of the 1p/19q allelic constitution in a pediatric anaplastic (oligodendro)-glioma showed homozygous co-deletion for markers: TNFRSF4 (located at 1p36.33), TP73 (1p36.32), PPAP2B (1pter-p22.1), DPYD (1p21.3), and PDCD5 (19q13.12), and hemizygous deletion of BAX (19q13.3-q13.4). No sequence changes for R132 and R172 of the IDH1/2 genes were identified. The molecular findings in this pediatric anaplastic glioma do not allow for a clearly definitive pathological diagnosis. However, the findings provide data on a number of 1p/19q genomic regions that, because of homozygotic deletion, might be the location of genes that are important for the development and clinical evolution of some malignant gliomas in children.
    Full-text · Article · Jan 2014
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