Inda María Mar, Mercapide Javier, Muñoz Jorge, Coullin Philippe, Danglot Giséle, Tuñon Teresa, Martínez-Peñuela José María, Rivera José María, Burgos Juan J, Bernheim Alain, Castresana Javier S
Laboratorio de Neuro-Oncología Molecular, Universidad de Navarra, 31008 Pamplona, Spain.
Oncol Rep. 2004 Dec;12(6):1341-7.
Medulloblastoma, which accounts for 20-25% of all childhood brain tumors, is defined as a primitive neuroectodermal tumor (PNET) located in the cerebellum. Supratentorial PNET are less frequent than medulloblastoma. But their clinical outcome is worse than in medulloblastomas. Chromosome 10q contains at least 2 tumor suppressor genes that might play a role in brain tumor development: PTEN and DMBT1. The aim of this study was to compare the status of homozygous deletion and expression of PTEN and DMBT1 genes in PNET primary tumor samples and cell lines. Homozygous deletions of PTEN and DMBT1 were studied in 32 paraffin-embedded PNET samples (23 medulloblastomas and 9 supratentorial PNET) and in 7 PNET cell lines, by differential PCR and by FISH. PTEN homozygous losses were demonstrated in 7 medulloblastomas (32%) and in no supratentorial PNET, while homozygous deletions of DMBT1 appeared in 1 supratentorial PNET (20%) and in 7 medulloblastomas (33%). No homozygous deletion of PTEN or DMBT1 was detected in any of the PNET cell lines either by differential PCR or by FISH. Expression study of the 2 genes was performed in the 7 PNET cell lines by RT-PCR. One PNET cell line lacked PTEN and DMBT1 expression, while 2 medulloblastoma cell lines did not express DMBT1. Our results add some positive data to the hypothesis that supratentorial PNETs and medulloblastomas might be genetically different.
髓母细胞瘤占儿童脑肿瘤的20% - 25%，被定义为位于小脑的原始神经外胚层肿瘤（PNET）。幕上PNET比髓母细胞瘤少见。但其临床预后比髓母细胞瘤差。10号染色体长臂至少包含2个可能在脑肿瘤发生中起作用的抑癌基因：PTEN和DMBT1。本研究的目的是比较PNET原发肿瘤样本和细胞系中PTEN和DMBT1基因的纯合缺失状态及表达情况。通过差异PCR和荧光原位杂交（FISH）技术，在32个石蜡包埋的PNET样本（23个髓母细胞瘤和9个幕上PNET）及7个PNET细胞系中研究了PTEN和DMBT1的纯合缺失情况。7个髓母细胞瘤（32%）检测到PTEN纯合缺失，幕上PNET未检测到；1个幕上PNET（20%）和7个髓母细胞瘤（33%）检测到DMBT1纯合缺失。通过差异PCR或FISH在任何PNET细胞系中均未检测到PTEN或DMBT1的纯合缺失。通过逆转录PCR（RT-PCR）在7个PNET细胞系中进行了这2个基因的表达研究。1个PNET细胞系缺乏PTEN和DMBT1表达，2个髓母细胞瘤细胞系不表达DMBT1。我们的结果为幕上PNET和髓母细胞瘤可能存在基因差异这一假说增添了一些阳性数据。
