6086 Background: For most patients with recurrent or metastatic salivary gland cancer (RM-SGC), there are no standard therapies. Many patients undergo genomic profiling to guide selection of targeted therapy. The MSK-IMPACT study applied a 468 gene next generation sequencing (NGS) panel, identifying actionable mutations in 34/114 patients (30%) with RM-SGC. Minimising cost will facilitate application within publically funded healthcare systems. We therefore sought to determine the utility of genomic profiling using a focused 24 gene targeted NGS panel to identify actionable mutations in RM-SGC with a sub-group analysis in adenoid cystic carcinoma (ACC) and non-ACC sub-types. Methods: From January 2017 to 2018, 125 patients with RM-SGC provided informed consent to an ethically approved study. Clinical and demographic characteristics were collected. DNA was extracted from FFPE samples and analysed using Qiagen GeneRead DNAseq Targeted Panel V2 in the Manchester Centre for Genomic Medicine Diagnostic Laboratory, an NHS clinically accredited lab. A custom bioinformatic pipeline was validated to detect single nucleotide variants and indels ( < 40bp) to 5% mutant allele frequency. Alterations were categorised following American College of Medical Genetics guidelines and Association for Molecular Pathology tiering. Results: DNA from 101 tumours (69 major, 32 minor salivary gland) was sequenced with 95% coverage at > 350x read depth over the target enrichment. 65 patients had adenoid cystic carcinoma (ACC) and 36 had non-ACC SGC. Median age was 55 years (range 18-80). 43 actionable alterations were identified in 33 patients within the following genes: TP53 (21%), PIK3CA (8%), ERBB2 (6%), PTEN (3%), BRAF (2%), EGFR (T790M) (1%), and AKT1 (1%). Targeted therapy was selected based on genomic findings in 12% of these patients. In ACC patients, actionable alterations were seen in 25% compared with 55% of non-ACC patients (9 adenocarcinoma, 5 salivary duct carcinoma, 3 carcinoma ex pleomorphic adenoma, 2 mucoepidermoid carcinoma and 1 myoepithelial carcinoma). Conclusions: This study identified actionable alterations in 33% of SGC patients using focused genomic profiling, demonstrating comparable utility to larger research panels. This focussed panel is being expanded to include emerging biomarkers such as NOTCH gene mutations, with NOTCH inhibitors currently in trials in ACC. Greater access to basket studies incorporating therapies matched to genomic alterations will maximise the clinical utility of this approach.
Role of apoptotic, autophagic and senescence pathways in minor salivary gland adenoid cystic carcinoma
