Genetic alterations in childhood medulloblastoma analyzed by comparative genomic hybridization.
Despite intensive therapy, the survival of children with medulloblastoma remains disappointing. Moreover, children who survive are affected by serious long-term sequelae of treatment that impair their quality of life. In search of chromosomal aberrations indicative of sites involved in oncogenic transformation and in an attempt to find reliable prognostic markers, the authors analyzed 15 medulloblastomas by comparative genomic hybridization. All neoplasms showed chromosomal abnormalities. The most frequent losses were 17p (7/15 tumors), 8p and 11p (6/15), 10p, 1lq, 16q, and 20q (5/15), and 20p (4/15). Gains were recurrently found at 7q (10/15 tumors), 17q and 18q (9/15 tumors), 7p and 13q (7/15), 18p (6/15), and 1q, 4q, 6q. and 9p (5/15 tumors). Four tumors showed loss of 17p together with gain of 17q, suggesting an isochromosome 17q. High-level amplifications were seen at 1p34, 5p15, 13q34, and 18p11 (one tumor each), and at 2p15 in two tumors, one of which was proven to be N-Myc amplification. The overall pattern of alterations found in this study confirms the findings of other studies and adds two novel regions with chromosomal gains, at 13q and 18q. Previous reports on the relation between 17q gain and survival could not be confirmed, whereas amplification of N-myc or L-myc seems to indicate poor clinical outcome.
Michiels
Erna M C
EM
Department of Pediatric Oncology, Emma Kinderziekenhuis/Academic Medical Center, Amsterdam, The Netherlands.
Weiss
Marjan M
MM
Hoovers
Jan M N
JM
Baak
Jan P A
JP
Voûte
P A
PA
Baas
Frank
F
Hermsen
Mario A J A
MA
D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D009693:Nucleic Acid Hybridization
D004273:DNA, Neoplasm