title: FGF4 and INT2 oncogenes are amplified and expressed in Kaposi's sarcoma.
abstract: Kaposi's sarcoma (KS) is a vascular tumor, the pathogenesis of which has been suggested to include human herpesvirus 8 (HHV-8) as well as various cytokines and growth factors. Very little is known about cytogenetic and molecular genetic changes in KS. We studied DNA copy number changes in KS and found a recurrent gain at 11q13. We then analyzed the amplification and expression status of two known oncogenes, FGF4 and INT2, residing at 11q13. Comparative genomic hybridization, interphase fluorescence in situ hybridization with yeast artificial chromosome probes containing FGF4 and INT2, and immunoperoxidase immunostaining with anti-FGF4 and -INT2 antibodies were used on 12 KS samples. All samples tested were shown by polymerase chain reaction to be HHV-8 positive. A recurrent gain at 11q13 was shown by comparative genomic hybridization in 4 of 10 cases studied. Of six cases studied by interphase fluorescence in situ hybridization, four showed a 3- to 4-fold amplification with the probes containing FGF4 and INT2. Expression of FGF4 and INT2 was found in nine and three cases, respectively, of nine studied. Amplification and expression of these genes is particularly interesting in the context of oncovirus involvement, because INT2 is a homolog of mouse int2 which causes mammary carcinoma in mice when activated by integration of retrovirus mouse mammary tumor virus. This raises the question of whether HHV-8 represents an integrating oncovirus that causes amplification and activation of genomic oncogenes in humans.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Kiuru-Kuhlefelt
authors.forename: M
authors.initials: M
authors.lastname: Sarlomo-Rikala
authors.forename: M L
authors.initials: ML
authors.lastname: Larramendy
authors.forename: M
authors.initials: M
authors.lastname: Söderlund
authors.forename: K
authors.initials: K
authors.lastname: Hedman
authors.forename: M
authors.initials: M
authors.lastname: Miettinen
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D019288:Herpesvirus 8, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000378:metabolism / Q000821:virology
chemical_list: D004273:DNA, Neoplasm; C496444:FGF3 protein, human; C496445:FGF4 protein, human; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors