title: Patterns of gene amplification in gastrointestinal stromal tumors (GIST).
abstract: Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal tumors of the gastrointestinal tract (GIT). They represent a wide clinico-pathological spectrum of tumors. No single histological or clinical parameter can predict the prognosis while the response to therapy is related to the type of KIT or PDGFRA mutation. Cytogenetic and CGH studies have identified frequent gross chromosomal aberrations but the target genes of these changes are unknown. To determine whether known oncogenes take part in genomic rearrangements and to investigate the potential clinical significance of their amplifications, nine known oncogenes (CMYC, MDM2, GLI1, CDK4, HER2, EGFR1, CCND1, FGF3, EMS) were analyzed by fluorescent in situ hybridization (FISH) on a tissue microarray (TMA) containing 94 primary GIST. Clinical follow-up information was available for 57 of these patients. Amplification was found for CMYC in three of 90 (3.3%), for MDM2 in five of 94 (5.3%), for EGFR1 in five of 94 (5.3%), and for CCND1 in seven of 79 (8.9%) evaluable cases. No amplifications were seen for HER2, GLI1, CDK4, FGF3, and EMS. Amplifications of MDM2 and CCND1 were associated with clinical and histological malignancy. In conclusion, our data show that gene amplification does occur in a subset of GIST. Identification of MDM2/CCND1 amplification may represent another molecular feature that could help in the evaluation of the behavior of GISTs.
authors.affiliation: Institute of Pathology, University of Basel, CH-4003 Basel, Switzerland. tornillol@uhbs.ch
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Duchini
authors.forename: Vincenza
authors.initials: V
authors.lastname: Carafa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.forename: Stefan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: Dolores
authors.initials: D
authors.lastname: Di Vizio
authors.forename: Amedeo
authors.initials: A
authors.lastname: Boscaino
authors.forename: Rosanna
authors.initials: R
authors.lastname: Russo
authors.forename: Coya
authors.initials: C
authors.lastname: Tapia
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Luigi
authors.initials: L
authors.lastname: Insabato
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009372:Neoplasms, Connective Tissue / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes / Q000235:genetics*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis