Patterns of gene amplification in gastrointestinal stromal tumors (GIST)

• Published in: Laboratory investigation 2005-07, Vol.85 (7), p.921-931
• Main Authors: Tornillo, Luigi, Duchini, Giacomo, Carafa, Vincenza, Lugli, Alessandro, Dirnhofer, Stefan, Di Vizio, Dolores, Boscaino, Amedeo, Russo, Rosanna, Tapia, Coya, Schneider-Stock, Regine, Sauter, Guido, Insabato, Luigi, Terracciano, Luigi M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biotechnology; Female; Fundamental and applied biological sciences. Psychology; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - metabolism; Gastrointestinal Stromal Tumors - pathology; Gene Amplification; Humans; In Situ Hybridization, Fluorescence; Investigative techniques, diagnostic techniques (general aspects); Laboratory Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasms, Connective Tissue - genetics; Neoplasms, Connective Tissue - metabolism; Neoplasms, Connective Tissue - pathology; Oncogenes - genetics; Pathology; research-article; Stromal Cells - metabolism; Stromal Cells - pathology; Tissue Array Analysis
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700284

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.