Deletion mapping and candidate gene analysis of chromosome 17 in primitive neuroectodermal tumors of the CNS
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文摘
The most frequent chromosomal abnormality in pediatric PNETs of the central nervous system is an i(17q). Molecular studies have confirmed LOH of 17p in PNETs and suggest that a region in 17p13, distal to p53, contains a tumor-suppressor gene. As a rapid means of identifying tumors with deletions of 17p, and specifically an i(17q), we have utilized two-color interphase FISH on primary brain tumor specimens. Thirty-six PNETs were analyzed with a series of chromosome 17-specific cosmids. The copy number for each 17p and 17q probe was determined relative to the number of signals for the 17 centromere probe. Karyotypes were prepared from each case for comparison with the FISH results. Cytogenetic studies were successful in 21 of 36 cases. Results demonstrated deletion of 17p in 2 cases and an i(17q) in 10 cases, which were confirmed by FISH. Two additional cases with deletion of 17p and 5 tumors with an i(17q) were demonstrated by FISH alone. Loss of 17p was seen in a total of 19 of the 36 (53 % ) PNETs. FISH with chromosome 17-specific cosmids is a useful adjunct to the pathologic diagnosis of PNETs, and will enable us to define a critical region on 17p which should contain a tumor-related gene. Pigment epithelium derived factor (PEDF) is a member of the serpin gene family. It maps to 17p13 and has been shown to induce neuronal differentiation in Y79 retinoblastoma cells. We have recently initiated studies to explore the potential role of PEDF as a candidate gene for PNETs. We developed SSCP assays for each of the 8 exons of the PEDF gene, and identified polymorphisms in exons 4 and 7. Loss of heterozygosity for exons 4 or 7 was demonstrated in 10 of 20 PNETs. Matched normal blood and tumor DNAs are being sequenced to determine if there are mutations in the coding sequence.