Loss of Heterozygosity Analysis of PTEN and DMBT1 Loci in Pediatric Brain Tumors / 대한소아혈액종양학회지

ABSTRACT

PURPOSE: PTEN and DMBT1, candidate tumor suppressor genes on chromosome 10q, were identified based on deletions in glioblastoma and medulloblastoma cell lines. We examined the occurrences and frequencies of allelic deletions on chromosome 10q23 and 10q25 by loss of heterozygosity (LOH) analysis in 24 pediatric brain tumors to investigate the possible involvement of PTEN and DMBT1 gene deletions in the development of pediatric brain tumors. METHOD: LOH was analyzed by polymerase chain reaction (PCR) of PTEN locus on 10q23 using 2 microsatellite markers, D10S608 and D10S579, and of DMBT1 locus on 10q25-q26.1 using a microsatellite marker, D10S587, in 24 pediatric brain tumor (18 medulloblastomas, 3 ependymomas, 2 glioblastomas and 1 supratentorial primitive neuroectodermal tumor) DNAs extracted from archival tissue specimens (case 1-15, 19) or fresh frozen tissue specimens (case 16-18, 20-24). RESULTS: Allelic deletions were detected in 4 of 23 informative cases (17%) on D10S608, 6 of 24 informative cases (25%) on D10S579, and 8 of 24 informative cases (33%) on D10S587. Overall 11 of 24 cases (46%) showed LOH on chromosome 10q at PTEN or DMBT1 loci, and they were 10 medulloblastomas and 1 ependymoma pathologically. Of 18 medulloblastomas, 7 (39%) exhibited LOH at PTEN locus, 8 (44%) exhibited LOH at DMBT1 locus, and 10 (56%) exhibited LOH at one or both of loci. CONCLUSION: Our results support the notion that PTEN and DMBT1 tumor suppressor gene deletions may be involved in the pathogenesis of pediatric brain tumors. Our results also suggested that PTEN and DMBT1 tumor suppressor gene deletions may not be important in molecular mechanism of glioblastoma development in children as in adults.