Orellana C, Hernandez-Martí M, Martínez F, Castel V, Millán J M, Alvarez-Garijo J A, Prieto F, Badía L
Unidad de Genetica, Hospital Universitario La Fe, Valencia, Spain.
Cancer Genet Cytogenet. 1998 Apr 15;102(2):93-9. doi: 10.1016/s0165-4608(97)00343-9.
Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated material losses of 17p, the region that contains the TP53 gene, as the most frequent abnormality. Mutations in the TP53 gene are, however, very rare in these tumors. These findings strongly suggest that another, as yet unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by single-strand conformational polymorphism analysis on 41 pediatric brain tumor samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2 astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were limited to more distal markers. On the other hand, TP53 mutations were detected in 6 of 41 samples studied. Our results not only confirm the low penetrance of the TP53 gene on pediatric CNS tumors, but also provide further evidence of a putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926) and 17pter, specifically taking part in the development of PNET.
对中枢神经系统（CNS）原始神经外胚层肿瘤（PNETs）的细胞遗传学和分子分析表明，17p区域（包含TP53基因）的物质缺失是最常见的异常情况。然而，TP53基因的突变在这些肿瘤中非常罕见。这些发现强烈表明，17p上另一个尚未确定的基因可能参与其中。我们通过微卫星标记对26例儿童中枢神经系统肿瘤进行了17p杂合性缺失（LOH）检测，并通过单链构象多态性分析对41例不同组织学类型的小儿脑肿瘤样本进行了TP53基因突变（外显子5 - 8）检测。在10例病例中检测到LOH：7例PNET、2例星形细胞瘤和1例多形性胶质母细胞瘤。在4例PNET中，缺失仅限于更远端的标记。另一方面，在所研究的41个样本中有6个检测到TP53突变。我们的结果不仅证实了TP53基因在小儿中枢神经系统肿瘤中的低外显率，还进一步证明了在标记（D17S938、D17S926）和17pter之间，TP53远端存在一个假定的肿瘤抑制基因，该基因特别参与了PNET的发生发展。
