Clinical utility of fluorescence in situ hybridization (FISH) in nonbrainstem glioblastomas of childhood

Clinical utility of fluorescence in situ hybridization (FISH) in nonbrainstem glioblastomas of childhood
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DOI:
10.1038/modpathol.3800415
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发表时间:
2005-09-01
期刊:
影响因子:
7.5
通讯作者:
Golanov, A
Golanov, A
中科院分区:
医学1区
文献类型:
--
作者:
Korshunov, A;Sycheva, R;Golanov, A

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星形细胞胶质瘤是最常见的儿童脑肿瘤;然而,与成人脑胶质母细胞瘤相比,非脑干胶质母细胞瘤极为罕见。关于各种分子标志物在儿童IV级星形细胞瘤中的临床意义的信息很少。本研究对44例非脑干胶质母细胞瘤患儿的肿瘤标本进行了分子分析和临床病理对照研究。用10条商品染色体探针(1p36、1q25、着丝粒(CEP)7、EGFR、CEP9、9p21/p16、CEP10、10q23/PTEN、19p13和19q13)进行荧光原位杂交(FISH)。已公开的分子异常按频率从高到低依次为:多倍体7(72%)、10q23缺失(61%)、9p21缺失(52%)、1p36缺失(41%)、1q25获得(25%)、多倍体9(16%)、EGFR扩增(9%)、19q13缺失(5%)、多倍体19(5%)、1p36/19q13缺失(2%)。总生存期仅在10q23/PTEN基因缺失者明显缩短(LOG-RANK检验,P=0.00007)。经多因素分析,仅10q23基因座缺失达到独立的预后水平(危险性比=2.88;P=0.01)。其他分子异常患者的存活率没有显著差异。总之,10q23剂量的FISH分析应该被推荐为一种辅助实验室方法,允许对儿童胶质母细胞瘤进行进一步的临床细分。
Astrocytic gliomas are the most common pediatric brain tumors; however, nonbrainstem glioblastomas are extremely rare compared with their adult counterparts. Little information is available on the clinical significance of various molecular markers in pediatric grade IV astrocytomas. The current study was focused on the molecular analysis and clinico-pathological correlations in a set of 44 tumor samples obtained from pediatric patients with nonbrainstem glioblastomas. Fluorescence in situ hybridization (FISH) with a set of 10 commercial chromosome probes (1p36, 1q25, centromere (CEP) 7, EGFR, CEP9, 9p21/p16, CEP10, 10q23/PTEN, 19p13, and 19q13) was performed. Disclosed molecular abnormalities, in descending order of frequency, included polysomy 7 (72%), loss of 10q23 (61%), loss of 9p21 (52%), loss of 1p36 (41%), gain of 1q25 (25%), polysomy 9 (16%), EGFR amplification (9%), loss of 19q13 (5%), polysomy 19 (5%), and codeletion 1p36/19q13 (2%). The overall survival time was markedly shorter only for those patients whose lesions harbored deletion of 10q23/PTEN locus (log-rank test; P=0.00007). By multivariate analysis, only loss of 10q23 locus reached an independent level of prognostic value (hazard ratio =2.88; P=0.01). There were no significant differences in patient survival for other molecular abnormalities. In conclusion, a FISH analysis of 10q23 dosage should be recommended as an ancillary laboratory method that allows further clinical subdivision of pediatric glioblastomas.