Vékony Hedy, Röser Kerstin, Löning Thomas, Ylstra Bauke, Meijer Gerrit A, van Wieringen Wessel N, van de Wiel Mark A, Carvalho Beatriz, Kok Klaas, Leemans C René, van der Waal Isaäc, Bloemena Elisabeth
Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry (ACTA), VU University Medical Center, Amsterdam, The Netherlands.
Genes Chromosomes Cancer. 2009 Feb;48(2):202-12. doi: 10.1002/gcc.20631.
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.
涎腺肌上皮肿瘤是相对罕见的肿瘤，其临床病程不可预测。需要更多关于其基因谱的知识来识别疾病的新预测指标。在本研究中，我们对27例原发性肿瘤（15例肌上皮瘤和12例肌上皮癌）进行了基于全基因组微阵列的比较基因组杂交（阵列CGH）。我们旨在更详细地描绘已知的染色体畸变，并揭示良性肌上皮瘤和肌上皮癌之间的染色体差异。通过无监督层次聚类分析来分析DNA拷贝数畸变模式。良性和恶性肿瘤均显示出有限数量的染色体改变（中位数分别为5和7.5）。在两个肿瘤组中，高频增益（≥20%）主要见于生长因子和生长因子受体基因座（如血小板衍生生长因子、成纤维细胞生长因子受体和表皮生长因子受体）。在肌上皮瘤中，原钙黏蛋白区域检测到高频缺失（≥20%）。阵列CGH数据的聚类分析确定了三个簇。8号染色体长臂和17号染色体上的拷贝数差异将这些簇区分开来。簇1包含两种表型的混合（n = 10），簇2主要包括良性肿瘤（n = 10），簇3仅包含癌（n = 7）。恶性和良性肿瘤之间的监督分析显示，8号染色体长臂上一个36 Mbp的区域在恶性肿瘤中更频繁地获得（P = 0.007，错误发现率 = 0.05）。这是第一项在基因组水平上研究涎腺良性和恶性肌上皮肿瘤之间基因组差异的研究。基因组图谱的无监督和监督分析均显示8号染色体长臂与涎腺肌上皮瘤的恶性表型有关。
