Object: Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of the central nervous system are malignant, invasive embryonal tumors with predominantly neuronal differentiation that comprise 20% of pediatric brain tumors. Cytogenetic analysis has shown that alterations in chromosome 17, particularly the loss of 17p and the formation of isochromosome 17q, as well as the gain of chromosome 7 are the most common changes among this group of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel regions of gain, loss, and amplification. The advent of more sophisticated multicolored fluorescence in situ hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits complete recognition of all aberrations including extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinations of classic banding analysis, FISH, CGH, and SKY to examine comprehensively the chromosomal aberrations present in this tumor group and to attempt to identify common structural rearrangement(s).
Methods: The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the tumors studied, which confirms data reported in the current literature. However, the authors have also combined the results of all three molecular cytogenetic assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal rearrangement (gained, lost, or involved in structural rearrangement).
Conclusions: The combined results indicate that chromosomes 7 and 17 are the most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, followed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identified in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally, desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher karyotype heterogeneity, amplification, and aneusomy than classic medulloblastomas.