High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma.
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.
Bernheim
Alain
A
Département de Biologie et de Pathologie Médicales, Institut de Cancérologie Gustave-Roussy, Villejuif, France.
Toujani
Saloua
S
Saulnier
Patrick
P
Robert
Thomas
T
Casiraghi
Odile
O
Validire
Pierre
P
Temam
Stéphane
S
Menard
Philippe
P
Dessen
Philippe
P
Fouret
Pierre
P
D000328:Adult; D001984:Bronchial Neoplasms / Q000235:genetics* / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000378:metabolism; D002869:Chromosome Aberrations; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2