Classic cytogenetic and comparative genomic hybridisation (CGH) data on osteosarcomas have been reported extensively in the literature. However, the number of paediatric osteosarcoma cases studied below the age of 14 years remains relatively small. This study reports four new cases of paediatric osteosarcoma in patients aged 3 to 13 years, evaluated by classic cytogenetics and CGH analyses. Clonal chromosomal alterations were detected in all the cases and included structural rearrangements at 1p11-13, 1q11, 4q27-33, 6p23-25, 6q16-25, 7p13-22, 7q11-36, 11p10-15, 11q23, 17p11.2-13, 21p11, and 21q11-22. The CGH analysis revealed recurrent gains at 1p, 4q, 17p, and 21q and losses at 3q and 16p. Five amplification sites were observed at 1q11-23, 6p21, 8q13, 8q21.3-24.2, and 17p. The data are discussed and compared with other cytogenetic reports in the literature.

Xq12-q13.3 duplication is a novel global developmental delay and autism-predisposing chromosomal aberration; pathogenesis of which may be mediated by increased dosage of genes contained in the duplication, including NLGN3, OPHN1, AR, EFNB1, TAF1, GJB1, and MED12.

Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors. Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridization to study 4 medulloblastoma cell lines and 1 xenograft. Cell line D-425 Med had a relatively simple karyotype, with a terminal deletion of 10q and amplification of MYC in double-minutes (dmins). FISH demonstrated that an apparent isochromosome (17q) by routine karyotyping was actually an unbalanced translocation between 2 copies of chromosome 17. Cell line D-556 Med also had a simple near-diploid stemline with an unbalanced 1;13 translocation resulting in a gain of 1q, an isochromosome (17q), and dmins. These findings were initially described using routine G-banded preparations, and FISH showed that the dmins were an amplification of MYC and the i(17q) was an isodicentric 17q chromosome. The other finding was confirmed by FISH, SKY, and comparative genomic hybridization. Cell lines D-721 Med and D-581 Med had complex karyotypic patterns that could be completely characterized only when FISH and SKY were used. Xenograft D-690 Med also had a complex pattern that FISH and SKY were helpful in completely elucidating. Interestingly, balanced reciprocal translocations were seen as well as complicated unbalanced translocations and marker chromosomes. Comparative genomic hybridization demonstrated only a deletion of 10q22-10q24, supporting the idea that despite the complexity of the chromosomal rearrangements, minimal alterations in the overall chromosomal content had occurred. This study demonstrates that routine cytogenetic preparations are adequate to describe chromosomal abnormalities in occasional medulloblastoma samples, but a broader spectrum of molecular cytogenetic methods is required to completely analyze most of these tumor samples.

Loss of portions of chromosome 17p, usually through the formation of i(17qp) is a well-known finding in medulloblastomas. Loss of heterozygosity (LOH) studies, however, occasionally demonstrate loss of the more distal portions of 17p, a pattern which is more consistent with a terminal deletion. Here we use a combination of routine karyotyping, fluorescence in situ hybridization (FISH) and LOH studies on four medulloblastoma cell lines and one xenograft to demonstrate the spectrum of chromosome 17 abnormalities which occur in these tumors. Cell line D-556 Med showed a typical dicentric i(17q) and cell line D-721 Med showed two normal copies of chromosome 17 by all methods. Cell line D-425 Med showed loss of terminal 17p by LOH, while the karyotype showed what appeared to be an i(17q). FISH and chromosome 17 painting, however, demonstrated that the abnormal chromosome 17 was actually formed through an unbalanced translocation involving two copies of chromosome 17, with breakpoints at p12 and q11-1, an explanation which reconciled the cytogenetic and LOH findings. Cell line D 581 Med had a terminal deletion at 17p11.2. The finding of two cells with i(17q) in this case by interphase FISH suggests that the terminal deletion arose from breakage of an i(17q). Finally, xenograft D 690 Med showed LOH for regions distal to 17p12, whereas karyotyping, FISH using probes on 17p, and chromosome 17 painting showed two intact copies of chromosome 17. This pattern can be explained by homologous recombination. These data support the concept that the critical deletion of 17p can occur through a variety of mechanisms in the medulloblastoma. The losses may occur through typical i(17q), as well as other mechanisms such as terminal deletions, possibly through breakage of i(17q), unbalanced translocations and homologous recombination.