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, C 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.

Segregation of non-p.R132H mutations inIDH1in distinct molecular subtypes of glioma

“…We first screened for combined LOH on 1p and 19q; chromosomal losses that are frequently observed in oligodendrogliomas and relatively rare in astrocytic tumors (Ohgaki and Kleihues 2009;Bromberg and van den Bent 2009)). These losses are caused by an unbalanced translocation between chromosomes 1 and 19 [t(1;19)(q10,p10)] (Griffin et al, 2006;Jenkins et al, 2006). In our entire dataset, 1p/19q LOH was determined in 317 (63.9%) samples.…”

Perfusion and diffusion MRI signatures in histologic and genetic subtypes of WHO grade II–III diffuse gliomas

“…In 2016, the WHO glioma classification scheme was restructured to reflect two common molecular alterations in gliomas: 1p/19q codeletion (1p19q − ) and isocitrate dehydrogenase-1 mutation (IDH MUT ) [7]. Co-deletion of 1p and 19q is most commonly associated with oligodendroglial tumors [8,9] and is both predictive of therapeutic response and prognostic for survival [10,11]. IDH mutations, which are known to be a driver mutation in low-grade gliomas [12,13], are associated with more favorable outcomes as they are known to be more sensitive to chemoradiation [14,15].…”

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

“…Up to 80% of oligodendrogliomas and B50% of oligoastrocytomas show combined deletions of the chromosomal arms 1p and 19q (Reifenberger and Louis, 2003) mediated by an unbalanced t(1;19)(q10;p10) translocation (Griffin et al, 2006;Jenkins et al, 2006). Deletion of 1p/19q was reported as an independent marker for favourable outcome in patients with anaplastic gliomas treated with chemotherapy and/or radiotherapy (van den Bent et al, 2005;Cairncross et al, 2006;Wick et al, 2009).…”