Abstract
<div>Abstract<p><b>Purpose:</b> The objectives of this study were to determine the incidence of the <i>MYB-NFIB</i> fusion in salivary adenoid cystic carcinoma (ACC), to establish the clinicopathologic significance of the fusion, and to analyze the expression of <i>MYB</i> in ACCs in the context of the <i>MYB-NFIB</i> fusion.</p><p><b>Experimental Design:</b> We did an extensive analysis involving 123 cancers of the salivary gland, including primary and metastatic ACCs, and non-ACC salivary carcinomas. <i>MYB-NFIB</i> fusions were identified by reverse transcriptase-PCR (RT-PCR) and sequencing of the RT-PCR products, and confirmed by fluorescence <i>in situ</i> hybridization. <i>MYB</i> RNA expression was determined by quantitative RT-PCR and protein expression was analyzed by immunohistochemistry.</p><p><b>Results:</b> The <i>MYB-NFIB</i> fusion was detected in 28% primary and 35% metastatic ACCs, but not in any of the non-ACC salivary carcinomas analyzed. Different exons in both the <i>MYB</i> and <i>NFIB</i> genes were involved in the fusions, resulting in expression of multiple chimeric variants. Notably, <i>MYB</i> was overexpressed in the vast majority of the ACCs, although <i>MYB</i> expression was significantly higher in tumors carrying the <i>MYB-NFIB</i> fusion. The presence of the <i>MYB-NFIB</i> fusion was significantly associated (<i>P</i> = 0.03) with patients older than 50 years of age. No correlation with other clinicopathologic markers, factors, and survival was found.</p><p><b>Conclusions:</b> We conclude that the <i>MYB-NFIB</i> fusion characterizes a subset of ACCs and contributes to <i>MYB</i> overexpression. Additional mechanisms may be involved in <i>MYB</i> overexpression in ACCs lacking the <i>MYB-NFIB </i>fusion. These findings suggest that <i>MYB</i> may be a specific novel target for tumor intervention in patients with ACC. Clin Cancer Res; 16(19); 4722–31. ©2010 AACR.</p></div>
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