title: Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study.
abstract: Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.
authors.affiliation: Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Niini
authors.forename: Ilari
authors.initials: I
authors.lastname: Scheinin
authors.forename: Leo
authors.initials: L
authors.lastname: Lahti
authors.forename: Suvi
authors.initials: S
authors.lastname: Savola
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Jaakko
authors.initials: J
authors.lastname: Hollmén
authors.forename: Tom
authors.initials: T
authors.lastname: Böhling
authors.forename: Aarne
authors.initials: A
authors.lastname: Kivioja
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Nord
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D001859:Bone Neoplasms / Q000097:blood / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002813:Chondrosarcoma / Q000097:blood / Q000235:genetics*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D008297:Male; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D015820:Cadherins; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase