title: Karyotypic evolution pathways in medulloblastoma/primitive neuroectodermal tumor determined with a combination of spectral karyotyping, G-banding, and fluorescence in situ hybridization.
abstract: Medulloblastomas (MBs) or primitive neuroectodermal tumors (PNETs) represent 15%-30% of pediatric brain tumors and are the most common brain tumors in children; they are rare in adults. Classification of these tumors is based on tissue morphology and is often controversial and problematic. Karyotypic analysis of these tumors using conventional cytogenetic methods is often a difficult process that may be hindered by a limited number of metaphase cells and poor chromosome morphology, often leading to only partial characterization of the chromosomal abnormalities. We investigated three primary human tumors and four cell lines (CHO-707, DAOY, D-341, and PFSK) utilizing a combination of conventional G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH) techniques. A high level of intratumoral heterogeneity was seen, with multiple numerical and structural chromosomal aberrations. The chromosomes most frequently involved in structural aberrations were chromosomes 1 (14 rearrangements), 7 (9 rearrangements), and 21 (9 rearrangements). The chromosomes most frequently involved in numerical aberrations were chromosomes 1, 12, and 13 (four cases) and chromosomes 14, 17, 19, 21, 22, and X (three cases). Numerous aberrant chromosomes were characterized only with the SKY analysis, and based on these findings multiple clones were identified, facilitating analysis of karyotypic evolution. The most frequent evolution mechanism was via polyploidization, followed by acquisition of additional numerical or structural aberrations (or both); however, the results showed that the karyotypic evolution process in these tumors is typically divergent and complex.
authors.affiliation: Department of Pediatric Hemato-Oncology and Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Ninette
authors.initials: N
authors.lastname: Cohen
authors.forename: David R
authors.initials: DR
authors.lastname: Betts
authors.forename: Uri
authors.initials: U
authors.lastname: Tavori
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
authors.forename: Tzvi
authors.initials: T
authors.lastname: Ram
authors.forename: Shlomi
authors.initials: S
authors.lastname: Constantini
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grotzer
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Luba
authors.initials: L
authors.lastname: Trakhtenbrot
mesh_terms: D000328:Adult; D005075:Biological Evolution; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002877:Chromosomes, Human / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008527:Medulloblastoma / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics*; D011003:Ploidies; D015398:Signal Transduction; D032681:Spectral Karyotyping; D014407:Tumor Cells, Cultured