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少突胶质细胞瘤中1p/19q联合缺失:预测性还是预后性生物标志物?

Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker?

作者信息

Weller Michael, Berger Hilmar, Hartmann Christian, Schramm Johannes, Westphal Manfred, Simon Matthias, Goldbrunner Roland, Krex Dietmar, Steinbach Joachim P, Ostertag Christoph B, Loeffler Markus, Pietsch Torsten, von Deimling Andreas

机构信息

Department of General Neurology, University of Tübingen, Tübingen, Germany.

出版信息

Clin Cancer Res. 2007 Dec 1;13(23):6933-7. doi: 10.1158/1078-0432.CCR-07-0573.

Abstract

PURPOSE

The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy.

EXPERIMENTAL DESIGN

Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification.

RESULTS

After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender.

CONCLUSIONS

Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.

摘要

目的

1号染色体短臂(1p)和19号染色体长臂(19q)遗传物质的联合缺失与世界卫生组织(WHO)3级间变性少突胶质细胞瘤患者的良好预后密切相关。1p/19q缺失在WHO 2级少突胶质细胞瘤中的预后价值尚不明确。重要的是,尚未对未接受放疗或化疗的患者中1p/19q联合缺失的可能影响进行研究。

实验设计

确定了76例少突胶质细胞瘤(n = 33)、少突星形细胞瘤(n = 30)、间变性少突胶质细胞瘤(n = 6)或间变性少突星形细胞瘤(n = 7)患者,这些患者在首次手术后直至随访结束或直至首次病情进展均未接受放疗或化疗,且有可供检测1p/19q状态的组织。通过多重连接依赖探针扩增法评估1p/19q状态。

结果

中位随访3.8年后,34例患者出现疾病进展。估计的无进展生存期中位数为4.6年。76例患者中有58例存在1p和19q联合缺失。在对组织学、切除范围和性别进行多变量调整后,1p/19q联合缺失的有无对无进展生存期并无预后意义。

结论

对于未接受放疗或化疗的少突胶质细胞瘤患者,1p/19q联合缺失不是一个敏感的预后生物标志物。由于这种共同缺失而丢失的基因产物可能包括对基因毒性疗法耐药的介质。或者,1p/19q缺失可能是促进胶质肿瘤形成的早期致癌病变,这些肿瘤对基因毒性应激仍保持高度敏感性。

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