Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping

Object. Medulloblastomas and related primitive neuroectodermal tumors (PNET s) of the central nervous system are malignant, invasive embryonal tumors w ith predominantly neuronal differentiation that comprise 20% of pediatric b rain 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 gr oup of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel region s of gain, loss, and amplification. The advent of more sophisticated multic olored fluorescence in situ hybridization (FISH) procedures such as spectra l karyotyping (SKY) now permits complete recognition of all aberrations inc luding extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinati ons of classic banding analysis, FISH, CGH, and SKY to examine comprehensiv ely 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 rearr angement). Conclusions. The combined results indicate that chromosomes 7 and 17 are th e most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 1 0 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, follow ed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tum ors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identifie d in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Add itionally, desmoplastic medulloblastomas and large-cell medulloblastomas ex hibited higher karyotype heterogeneity, amplification, and aneusomy than cl assic medulloblastomas.