Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas

H. Vekony, K Röser, T Löning, B. Ijlstra, G.A. Meijer, W.N. van Wieringen, M.A. van de Wiel, B. Pinto Morais de Carvalho, K. Kok, C.R. Leemans, I. van der Waal, E. Bloemena

Research output: Contribution to JournalArticleAcademicpeer-review

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 (≥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 (≥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. © 2008 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)202-212
JournalGenes, Chromosomes and Cancer
Volume48
DOIs
Publication statusPublished - 2009

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Myoepithelioma
Salivary Glands
Phenotype
Neoplasms
Carcinoma
Cluster Analysis
Chromosomes
Chromosomes, Human, Pair 17
Comparative Genomic Hybridization
Growth Factor Receptors
Cadherins
Chromosome Aberrations
Intercellular Signaling Peptides and Proteins
Genome
DNA

Cite this

Vekony, H. ; Röser, K ; Löning, T ; Ijlstra, B. ; Meijer, G.A. ; van Wieringen, W.N. ; van de Wiel, M.A. ; Pinto Morais de Carvalho, B. ; Kok, K. ; Leemans, C.R. ; van der Waal, I. ; Bloemena, E. / Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas. In: Genes, Chromosomes and Cancer. 2009 ; Vol. 48. pp. 202-212.
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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 (≥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 (≥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. {\circledC} 2008 Wiley-Liss, Inc.",
author = "H. Vekony and K R{\"o}ser and T L{\"o}ning and B. Ijlstra and G.A. Meijer and {van Wieringen}, W.N. and {van de Wiel}, M.A. and {Pinto Morais de Carvalho}, B. and K. Kok and C.R. Leemans and {van der Waal}, I. and E. Bloemena",
year = "2009",
doi = "10.1002/gcc.20631",
language = "English",
volume = "48",
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journal = "Genes, Chromosomes and Cancer",
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Vekony, H, Röser, K, Löning, T, Ijlstra, B, Meijer, GA, van Wieringen, WN, van de Wiel, MA, Pinto Morais de Carvalho, B, Kok, K, Leemans, CR, van der Waal, I & Bloemena, E 2009, 'Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas' Genes, Chromosomes and Cancer, vol. 48, pp. 202-212. https://doi.org/10.1002/gcc.20631

Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas. / Vekony, H.; Röser, K; Löning, T; Ijlstra, B.; Meijer, G.A.; van Wieringen, W.N.; van de Wiel, M.A.; Pinto Morais de Carvalho, B.; Kok, K.; Leemans, C.R.; van der Waal, I.; Bloemena, E.

In: Genes, Chromosomes and Cancer, Vol. 48, 2009, p. 202-212.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas

AU - Vekony, H.

AU - Röser, K

AU - Löning, T

AU - Ijlstra, B.

AU - Meijer, G.A.

AU - van Wieringen, W.N.

AU - van de Wiel, M.A.

AU - Pinto Morais de Carvalho, B.

AU - Kok, K.

AU - Leemans, C.R.

AU - van der Waal, I.

AU - Bloemena, E.

PY - 2009

Y1 - 2009

N2 - 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 (≥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 (≥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. © 2008 Wiley-Liss, Inc.

AB - 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 (≥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 (≥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. © 2008 Wiley-Liss, Inc.

U2 - 10.1002/gcc.20631

DO - 10.1002/gcc.20631

M3 - Article

VL - 48

SP - 202

EP - 212

JO - Genes, Chromosomes and Cancer

JF - Genes, Chromosomes and Cancer

SN - 1045-2257

ER -