Abstract

<div>Abstract<p><b>Purpose:</b> We sought to identify genomic alterations (GA) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS.</p><p><b>Experimental Design:</b> DNA was extracted from 149 tumors. Comprehensive genomic profiling (CGP) was performed on hybridization-captured adaptor ligation-based libraries of 182 or 315 cancer-related genes plus introns from 14 or 28 genes frequently rearranged for cancer and evaluated for all classes of GAs.</p><p><b>Results:</b> A total of 590 GAs were found in 157 unique genes (mean 3.9/tumor). GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (<i>P</i> = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; <i>P</i> = 0.043). <i>RAS</i> GAs were observed: adenocarcinoma, NOS (17.3%); SDC (26.8%); ca ex PA (4.2%); and carcinoma, NOS (9.4%; <i>P</i> = 0.054). <i>ERBB2</i> GAs, including amplifications and mutations, were common: adenocarcinoma, NOS (13.5%); SDC (26.8%); ca ex PA (29.2%); carcinoma, NOS (18.8; <i>P</i> = 0.249). Other notable GAs include <i>TP53</i> in >45% of each histotype; <i>NOTCH1</i>: adenocarcinoma, NOS (7.7%), ca ex PA (8.3%), carcinoma, NOS (21.6%); <i>NF1</i>: adenocarcinoma, NOS (9.6%), SDC (17.1%), carcinoma, NOS (18.8%). <i>RET</i> fusions were identified in one adenocarcinoma, NOS (<i>CCDC6-RET</i>) and two SDCs (<i>NCOA4-RET</i>). Clinical responses were observed in patients treated with anti-HER2 and anti-RET–targeted therapies.</p><p><b>Conclusions:</b> CGP of salivary adenocarcinoma, NOS, SDCs, ca ex PA, and carcinoma, NOS revealed diverse GAs that may lead to novel treatment options. <i>Clin Cancer Res; 22(24); 6061–8. ©2016 AACR</i>.</p></div>

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