title: Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.
abstract: Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.
authors.affiliation: Department of Clinical Genetics, University Hospital, Lund, Sweden. david.gisselsson@klingen.lu.se
authors.forename: David
authors.initials: D
authors.lastname: Gisselsson
authors.forename: Eva
authors.initials: E
authors.lastname: Pålsson
authors.forename: Mattias
authors.initials: M
authors.lastname: Höglund
authors.forename: Henryk
authors.initials: H
authors.lastname: Domanski
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Nikos
authors.initials: N
authors.lastname: Pandis
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002871:Chromosome Banding; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics; D007621:Karyotyping; D008297:Male; D008677:Metaphase / Q000235:genetics; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured