Jenkins Robert B, Blair Hilary, Ballman Karla V, Giannini Caterina, Arusell Robert M, Law Mark, Flynn Heather, Passe Sandra, Felten Sara, Brown Paul D, Shaw Edward G, Buckner Jan C
Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer Res. 2006 Oct 15;66(20):9852-61. doi: 10.1158/0008-5472.CAN-06-1796.
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.
1p和19q染色体联合缺失与间变性少突胶质细胞瘤患者预后改善及对治疗的反应性相关。这种缺失通常累及整条染色体臂,提示存在t(1;19)(q10;p10)。我们使用干细胞培养基培养了一些肿瘤。从梅奥诊所的21例患者以及参与北中部癌症治疗组(NCCTG)两项低级别胶质瘤试验的98例患者中获取石蜡包埋组织。CEP1和19p12探针的间期融合检测到了t(1;19)。通过荧光原位杂交评估1p/19q缺失情况。培养后,1例少突胶质细胞瘤含有一条不平衡的45,XX,t(1;19)(q10;p10)。在所有中期和74%的间期核中观察到CEP1/19p12融合。在梅奥诊所的少突胶质细胞瘤中,融合的发生率为81%。在NCCTG患者中,少突胶质细胞瘤、混合性少突星形细胞瘤和星形细胞瘤中CEP1/19p12融合的发生率分别为55%、47%和0%。NCCTG中91%的1p/19q缺失的胶质瘤和12%的无1p/19q缺失的胶质瘤有CEP1/19p12融合(P<0.001,卡方检验)。所有患者的总生存(OS)中位数在无融合时为8.1年,有融合时为11.9年(P = 0.003)。低级别少突胶质细胞瘤患者的OS中位数在无融合时为9.1年,有融合时为13.0年(P = 0.01)。对于有1p/19q联合缺失的患者也观察到了类似的显著OS中位数差异。对于接受较高剂量放疗的患者,无改变与显著更短的OS相关。我们的结果强烈提示t(1;19)(q10;p10)介导了人类胶质瘤中的1p/19q联合缺失。与1p/19q联合缺失一样,1;19易位与低级别胶质瘤患者更好的OS和无进展生存期相关。