title: Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone.
abstract: Molecular genetic studies on vascular tumors are rare. Recently, possible involvement of MYC and KDR has been documented in a subset of angiosarcomas of soft tissue. We performed a cytogenetic analysis of primary angiosarcomas of bone (n = 13) and soft tissue (n = 5) using high density array-comparative genomic hybridization (array-CGH). Regions of interest were validated by fluorescence in situ hybridization (FISH). Antibodies for candidate genes (SKI, MYC, KDR, and MAPK9) were selected and immunohistochemistry was performed. Six angiosarcomas of bone and four angiosarcomas of soft tissue showed chromosomal losses, gains, and high level amplifications. Cluster analysis identified two groups: a group with a complex genetic profile and a group with only few genetic aberrations. Five regions of interest were selected, which were located at chromosome bands 1p36.23, 2q32-34, 5q35, 8q24, and 17q21.32-24.2. Interphase FISH confirmed the high-level amplifications. Immunohistochemical analysis showed high expression of MYC (16/60), MAPK9 (63/69), and SKI (52/62). There were no differences between the two groups with regards to location, immunohistochemical expression nor survival. In summary, we identified two subgroups of angiosarcoma: those with few or no gross aberrations and those which show numerous genetic aberrations consisting of chromosomal losses, gains and high level amplifications or complex aberrations. The most common finding was amplification of 2q and 17q in both angiosarcoma of bone and soft tissue, suggesting overlap in tumorigenesis irrespective of their location. We show MYC amplification in primary angiosarcoma indicating this is not entirely specific for radiation-induced angiosarcoma.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sofie L J
authors.initials: SL
authors.lastname: Verbeke
authors.forename: Danielle
authors.initials: D
authors.lastname: de Jong
authors.forename: Franco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006394:Hemangiosarcoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C505827:MAP9 protein, human; C489427:MYC protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C060614:SKI protein, human