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少突胶质细胞瘤患者中与总生存期较短相关的基因组畸变的鉴定。

Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors.

作者信息

Trost Detlef, Ehrler Marion, Fimmers Rolf, Felsberg Jörg, Sabel Michael C, Kirsch Lutz, Schramm Johannes, Wiestler Otmar D, Reifenberger Guido, Weber Ruthild G

机构信息

Department of Human Genetics, Rheinische Friedrich-Wilhelms-University, Bonn, Germany.

出版信息

Int J Cancer. 2007 Jun 1;120(11):2368-76. doi: 10.1002/ijc.22574.

Abstract

Deletions on chromosomes 1p and 19q are associated with favorable prognosis in patients with oligodendroglial tumors. The aim of our study was to identify additional genomic aberrations linked to patient survival. We performed a genome-wide screen for genomic imbalances by comparative genomic hybridization on tumors from 70 patients, including 40 oligodendrogliomas, 30 oligoastrocytomas (21 WHO grade II tumors, 49 WHO grade III tumors). Data were correlated with overall patient survival (OS, median follow-up: 5.8 years). The most frequent aberrations were losses on chromosome 19q (64%), 1p (59%), 9p (26%), 4q (21%), 10q (19%), 18q (17%); gains on 7q (24%), 19p (19%), 7p (17%). In univariate analyses, combined 1p/19q and 19q loss were significantly associated with longer OS, and gains on 7, 8q, 19q, 20, losses on 9p, 10, 18q, Xp with shorter OS. Multivariate analyses showed the most significant prognostic factors for OS of patients with any oligodendroglial tumor to be WHO grade [odds ratio (OR) 8], 7p gain (OR 6), 9p loss (OR 3); for OS of patients with anaplastic tumors to be 7p gain (OR 10), 8q gain (OR 5), 18q loss (OR 3). Patients with anaplastic oligodendroglial tumors containing one or more prognostically unfavorable genomic aberration had a poor outcome independent of the 1p/19q status. In summary, we identified several independent genomic markers of shorter survival in patients with oligodendroglial tumors. Thus, molecular diagnostic testing, which is usually restricted to 1p/19q deletion analysis, may need to be refined by additionally assessing the prognostically unfavorable genomic aberrations identified.

摘要

1p和19q染色体缺失与少突胶质细胞瘤患者的预后良好相关。我们研究的目的是确定与患者生存相关的其他基因组畸变。我们通过比较基因组杂交对70例患者的肿瘤进行全基因组筛查,以检测基因组失衡,其中包括40例少突胶质细胞瘤、30例少突星形细胞瘤(21例WHO二级肿瘤、49例WHO三级肿瘤)。数据与患者总生存期(OS,中位随访时间:5.8年)相关。最常见的畸变是19q染色体缺失(64%)、1p染色体缺失(59%)、9p染色体缺失(26%)、4q染色体缺失(21%)、10q染色体缺失(19%)、18q染色体缺失(17%);7q染色体增益(24%)、19p染色体增益(19%)、7p染色体增益(17%)。在单变量分析中,1p/19q联合缺失和19q缺失与更长的总生存期显著相关,而7、8q、19q、20号染色体增益,9p、10、18q、Xp染色体缺失与较短的总生存期相关。多变量分析显示,对于任何少突胶质细胞瘤患者,总生存期的最显著预后因素为WHO分级[比值比(OR)8]、7p增益(OR 6)、9p缺失(OR 3);对于间变性肿瘤患者,总生存期的最显著预后因素为7p增益(OR 10)、8q增益(OR 5)、18q缺失(OR 3)。含有一个或多个预后不良基因组畸变的间变性少突胶质细胞瘤患者,无论1p/19q状态如何,预后均较差。总之,我们确定了少突胶质细胞瘤患者中几个独立的生存期较短的基因组标志物。因此,通常仅限于1p/19q缺失分析的分子诊断检测,可能需要通过额外评估已确定的预后不良基因组畸变来加以完善。

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