Loss of Heterozygosity Analysis of Chromosome 17p13.1-13.3 and Its Correlation with Clinical Outcome in Medulloblastomas / 대한소아혈액종양학회지

ABSTRACT

PURPOSE: Cytogenetic studies molecular genetic studies, including loss of heterozygosity (LOH) studies, have shown that deletions on the short arm of chromosome 17 (17p) distal to TP53 locus are the most common genetic events in medulloblastoma, and that these occur in 30 to 50% of medulloblastomas. We examined the occurrences and frequencies of allelic deletions on chromosome 17p13.1-13.3 by 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. METHOD: LOH was analyzed by polymerase chain reaction (PCR) on chromosome 17p13.1-13.3 using 3 microsatellite markers, TP53 on 17p13.1, D17S796 on 17p13.1-13.2 and D17S1574 on 17p13.3, in 17 medulloblastoma DNAs extracted from archival tissue specimens (cases 1~15) or fresh frozen tissue specimens (cases 16 and 17). RESULTS: Allelic deletions were detected in 5 of 17 informative cases (29%) on TP53, 8 of 17 informative cases (47%) on D17S796, and 4 of 17 informative cases (24%) on D17S1574. Overall, 9 of 17 cases (53%) showed LOH on chromosome 17p13.1-13.3. The 5-year progression free survival (PFS) and 5-year overall survival (OS) rates were identical (59%). The 5-year PFS for 9 medulloblastoma patients with LOH on 17p13.1-13.3 was 56%, and the 5-year PFS for 8 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. CONCLUSION: 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.