Characterization of chromosome 17 abnormalities in medulloblastomas

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 portion s of 17p, a pattern which is more consistent with a terminal deletion. Here we use a combination of routine karyotyping, fluorescence in situ hybridiz ation (FISH) and LOH studies on four medulloblastoma cell lines and one xen ograft to demonstrate the spectrum of chromosome 17 abnormalities which occ ur in these tumors. Cell line D-556 Med showed a typical dicentric i(17q) a nd cell line D-721 Med showed two normal copies of chromosome 17 by all met hods. Cell line D-425 Med showed loss of terminal 17p by LOH, while the kar yotype showed what appeared to be an i(17q). FISH and chromosome 17 paintin g, however, demonstrated that the abnormal chromosome 17 was actually forme d through an unbalanced translocation involving two copies of chromosome 17 , with breakpoints at p12 and q11-1, an explanation which reconciled the cy togenetic 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 FI SH suggests that the terminal deletion arose from breakage of an i(17q). Fi nally, xenograft D 690 Med showed LOH for regions distal to 17p12, whereas karyotyping, FISH using probes on 17p, and chromosome 17 painting showed tw o intact copies of chromosome 17. This pattern can be explained by homologo us recombination. These data support the concept that the critical deletion of 17p can occur through a Variety of mechanisms in the medulloblastoma. T he losses may occur through typical i(17q), as well as other mechanisms suc h as terminal deletions, possibly through breakage of i(17q), unbalanced tr anslocations and homologous recombination.