title: Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas.
abstract: Salivary gland myoepithelial tumors are relatively uncommon tumors with an unpredictable clinical course. More knowledge about their genetic profiles is necessary to identify novel predictors of disease. In this study, we subjected 27 primary tumors (15 myoepitheliomas and 12 myoepithelial carcinomas) to genome-wide microarray-based comparative genomic hybridization (array CGH). We set out to delineate known chromosomal aberrations in more detail and to unravel chromosomal differences between benign myoepitheliomas and myoepithelial carcinomas. Patterns of DNA copy number aberrations were analyzed by unsupervised hierarchical cluster analysis. Both benign and malignant tumors revealed a limited amount of chromosomal alterations (median of 5 and 7.5, respectively). In both tumor groups, high frequency gains (> or =20%) were found mainly at loci of growth factors and growth factor receptors (e.g., PDGF, FGF(R)s, and EGFR). In myoepitheliomas, high frequency losses (> or =20%) were detected at regions of proto-cadherins. Cluster analysis of the array CGH data identified three clusters. Differential copy numbers on chromosome arm 8q and chromosome 17 set the clusters apart. Cluster 1 contained a mixture of the two phenotypes (n = 10), cluster 2 included mostly benign tumors (n = 10), and cluster 3 only contained carcinomas (n = 7). Supervised analysis between malignant and benign tumors revealed a 36 Mbp-region at 8q being more frequently gained in malignant tumors (P = 0.007, FDR = 0.05). This is the first study investigating genomic differences between benign and malignant myoepithelial tumors of the salivary glands at a genomic level. Both unsupervised and supervised analysis of the genomic profiles revealed chromosome arm 8q to be involved in the malignant phenotype of salivary gland myoepitheliomas.
authors.affiliation: Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry (ACTA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hedy
authors.initials: H
authors.lastname: Vékony
authors.forename: Kerstin
authors.initials: K
authors.lastname: Röser
authors.forename: Thomas
authors.initials: T
authors.lastname: Löning
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.forename: Mark A
authors.initials: MA
authors.lastname: van de Wiel
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carvalho
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.forename: Isaäc
authors.initials: I
authors.lastname: van der Waal
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
mesh_terms: D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009208:Myoepithelioma / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000235:genetics / Q000502:physiology; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D025521:Tumor Suppressor Proteins