High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma
| Autor: | Philippe Menard, Patrick Saulnier, Pierre Fouret, Alain Bernheim, Odile Casiraghi, Saloua Toujani, Philippe Dessen, Thomas Robert, Stéphane Temam, Pierre Validire |
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| Přispěvatelé: | Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomes et cancer (GC (FRE2939)), Laboratoire de Génétique Oncologique, Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2008 |
| Předmět: |
Male
MESH: Oncogenes Gene Dosage MESH: Carcinoma Adenoid Cystic MESH: Gene Dosage MESH: Salivary Gland Neoplasms MESH: Nucleic Acid Hybridization 0302 clinical medicine CDKN2A CDKN2B Genes Tumor Suppressor MESH: In Situ Hybridization Fluorescence MESH: Bronchial Neoplasms In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis 0303 health sciences MESH: Middle Aged biology Bronchial Neoplasms Nucleic Acid Hybridization Proto-Oncogene Proteins c-mdm2 Middle Aged Salivary Gland Neoplasms Carcinoma Adenoid Cystic Immunohistochemistry 030220 oncology & carcinogenesis Mdm2 Female Adult Tumor suppressor gene Adenoid cystic carcinoma [SDV.CAN]Life Sciences [q-bio]/Cancer PDGFRA Pathology and Forensic Medicine 03 medical and health sciences MESH: Proto-Oncogene Proteins c-mdm2 medicine MESH: Chromosome Aberrations Humans Molecular Biology neoplasms MESH: Genome Human 030304 developmental biology Chromosome Aberrations MESH: Humans Genome Human MESH: Adult MESH: Immunohistochemistry Cell Biology Oncogenes MESH: Genes Tumor Suppressor medicine.disease MESH: Male MESH: Gene Deletion MESH: Oligonucleotide Array Sequence Analysis biology.protein Cancer research Cyclin-dependent kinase 6 MESH: Female Gene Deletion Comparative genomic hybridization |
| Zdroj: | Laboratory Investigation Laboratory Investigation, Nature Publishing Group, 2008, 88 (5), pp.464-73. ⟨10.1038/labinvest.2008.18⟩ |
| ISSN: | 1530-0307 0023-6837 |
| DOI: | 10.1038/labinvest.2008.18⟩ |
| Popis: | Adenoid cystic carcinoma (ACC) is a rare but distinctive tumor. Oligonucleotide array comparative genomic hybridization has been applied for cataloging genomic copy number alterations (CNAs) in 17 frozen salivary or bronchial tumors. Only four whole chromosome CNAs were found, and most cases had 2–4 segmental CNAs. No high level amplification was observed. There were recurrent gains at 7p15.2, 17q21–25, and 22q11–13, and recurrent losses at 1p35, 6q22–25, 8q12–13, 9p21, 12q12–13, and 17p11–13. The minimal region of gain at 7p15.2 contained the HOXA cluster. The minimal common regions of deletions contained the CDKN2A/CDKN2B, TP53, and LIMA1 tumor suppressor genes. The recurrent deletion at 8q12.3–13.1 contained no straightforward tumor suppressor gene, but the MIRN124A2 microRNA gene, whose product regulates MMP2 and CDK6. Among unique CNAs, gains harbored CCND1, KIT/PDGFRA/KDR, MDM2, and JAK2. The CNAs involving CCND1, MDM2, KIT, CDKN2A/2B, and TP53 were validated by FISH and/or multiplex ligation-dependent probe amplification. Although most tumors overexpressed cyclin D1 compared with surrounding glands, the only case to overexpress MDM2 had the corresponding CNA. In conclusion, our report suggests that ACC is characterized by a relatively low level of structural complexity. Array CGH and immunohistochemical data implicate MDM2 as the oncogene targeted at 12q15. The gain at 4q12 warrants further exploration as it contains a cluster of receptor kinase genes (KIT/PDGFRA/KDR), whose products can be responsive to specific therapies. |
| Databáze: | OpenAIRE |
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