title: Loss of heterozygosity analysis of chromosome 17p13.1-13.3 and its correlation with clinical outcome in medulloblastomas.
abstract: Cytogenetic and molecular genetic studies have shown that deletions on the short arm of chromosome 17 distal to p53 locus are the most common genetic events in medulloblastoma. We examined the occurrences and frequencies of allelic deletions on chromosome 17p13.1-13.3 by loss of heterozygosity (LOH) analysis to investigate the possible involvement of 17p13.1-13.3 in medulloblastoma development. We also performed survival analysis to determine whether LOH analysis of 17p13.1-13.3 can be used to predict prognosis in medulloblastoma. Loss of heterozygosity was analyzed by polymerase chain reaction on chromosome 17p13.1-13.3 using three microsatellite markers, TP53 on 17p13.1, D17S796 on 17p13.1-13.2, and D17S1574 on 17p13.3, in 17 medulloblastoma DNAs extracted either from archival tissue or fresh frozen tissue specimens. Allelic deletions were detected in five of 17 informative cases (29%) on TP53, eight of 17 informative cases (47%) on D17S796, and four of 17 informative cases (24%) on D17S1574. Overall, nine of 17 cases (53%) showed LOH on chromosome 17p13.1-13.3. The 5-year progression free survival (PFS) and 5-year overall survival rates were identical (59%). The 5-year PFS for nine medulloblastoma patients with LOH on 17p13.1-13.3 was 56%, and the 5-year PFS for eight medulloblastoma patients without LOH on 17p13.1-13.3 was 63%. In our survival analysis, we did not find a significant association between survival and LOH on 17p13.1-13.3. Our results support the notion that deletions of chromosome 17p13.1-13.3 may be involved in the pathogenesis of medulloblastoma. From survival analysis, we conclude that LOH on chromosome 17p13.1-13.3 may not be a significant predictor of prognosis in medulloblastoma.
authors.affiliation: Department of Pediatrics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Jung
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Byung-Kyu
authors.initials: BK
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D002648:Child; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000401:mortality; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011379:Prognosis