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
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.
- SourceAvailable from: Bjoern Tews
[Show abstract] [Hide abstract]
- "Oligodendroglial tumours are primary central nervous system tumours that account for B10–15% of all gliomas and comprise four histologically defined entities, namely well-differentiated oligodendrogliomas of World health organization (WHO) grade II, anaplastic oligodendrogliomas (WHO grade III), mixed oligoastrocytomas (WHO grade II) and anaplastic oligoastrocytomas (WHO grade III) (Louis et al., 2007). 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). "
ABSTRACT: Deletions of chromosomal arms 1p and 19q are frequent in oligodendroglial tumours and linked to radio- and chemotherapy response as well as longer survival. The molecular mechanisms underlying this clinically important association are as yet unknown. Here, we studied the peroxiredoxin 1 (PRDX1) gene at 1p34.1 for promoter methylation and expression in primary gliomas and investigated its role in radio- and chemosensitivity of glioma cells in vitro. In total, we screened primary glioma tissues from 93 patients for methylation of the 5'-CpG island of PRDX1 by sodium bisulfite sequencing. PRDX1 mRNA and protein expression levels were determined in subsets of the tumours by quantitative PCR and western blot analysis, respectively. PRDX1 hypermethylation and reduced expression were frequently detected in oligodendroglial tumours and secondary glioblastomas, but not in primary glioblastomas. In oligodendroglial tumours, both PRDX1 hypermethylation and reduced mRNA expression were significantly associated with 1p/19q-deletion. Stable knockdown of PRDX1 by lentiviral transduction of short-hairpin (sh)RNA constructs significantly increased apoptosis and reduced cell viability of Hs683 glioma cells exposed to ionizing irradiation or temozolomide in vitro. Taken together, our findings indicate that epigenetic silencing of PRDX1 is frequent in 1p/19q-deleted oligodendroglial tumours and likely contributes to radio- and chemosensitivity of these tumours.Oncogene 12/2011; 31(29):3409-18. DOI:10.1038/onc.2011.513 · 8.56 Impact Factor
- "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). "
Chapter: Molecular Hallmarks of GliomasMolecular Targets of CNS Tumors, 09/2011; , ISBN: 978-953-307-736-9
[Show abstract] [Hide abstract]
- "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  . 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 . "
ABSTRACT: Human aldo-keto reductase (AKR) 1C3, type 2 3α-hydroxysteroid dehydrogenase (HSC)/ type 5 17β-HSD, is known to be involved in steroids, prostaglandins, and lipid aldehydes metabolism. The expression of AKR1C3 has been demonstrated in hormone-dependent normal tissues such as breast, endometrium, prostate, and testis; and de -regulated AKR1C3 expression has been shown in breast carcinoma, endometrial hyperplasia, endometrial carcinoma, and prostate carcinoma. AKR1C3 expression has also been demonstrated in hormone-independent normal tissues (renal tubules and urothelium) and neoplastic tissues (renal cell carcinoma, Wilm's tumor, and urothelial cell carcinoma). Extensive expression of AKR1C3 in normal and neoplastic as well as hormone-dependent and hormone-independent tissues indicates that AKR1C3 may have functions beyond steroid hormone metabolism. In this report, we describe a widespread expression of AKR1C3 in glial neoplasms and meningiomas, with limited expression in medulloblastoma and no expression in Schwannoma. These tumors, except meningioma, are not classically considered to be sex hormone-dependent or related brain tumors. The current results corroborate our earlier observations that AKR1C3 is expressed in both sex hormone-dependent and hormone-independent malignancies. Similar to AKR1C3 distribution in Wilm's tumor, we also demonstrate that expression of AKR1C3 is reduced in tumors with embryonic phenotypes.International journal of clinical and experimental pathology 01/2010; 3(8):743-54. · 1.78 Impact Factor