Detection of novel genetic aberrations in salivary duct carcinoma (SDC) by SNaPshot analysis.

Abstract

5579 Background: Salivary gland cancers (SGCs) are rare and heterogeneous malignancies, with SDC being one of the more aggressive subtypes. Establishing effective therapy for SGCs is challenging given their rarity and heterogeneity. Cytotoxic chemotherapy has limited efficacy, and of the targeted therapies that have been studied, few objective responses have been seen. It is clear that disease management with targeted agents is most effective when directed by tumor genotype. To address this need, we utilized a clinical test, SNaPshot, designed to detect tumor-specific mutations to help direct treatment of SDC with targeted therapies. Methods: 24 SDC specimens were genotyped. These included 7 patients seen at the Massachusetts General Hospital Cancer Center who were prospectively tested. The SNaPshot assay uses DNA extracted from FFPE tissue and was designed to detect sequence variants in a panel of 14 clinically-relevant cancer genes. FISH was used to detect HER2 gene amplification. Retrospective review of clinical charts and of tumor pathological features was performed. Results: Mutually exclusive genetic aberrations were detected in 13 of 24 (54%) tumors, including 2 mutations in BRAF(8%), 4 mutations in PIK3CA (16%), and 7 cases of HER2 amplification (29%). Prospective clinical testing of 7 SDC identified mutations in 4 tumors, and influenced therapeutic decisions for 3 patients: 1 patient with a BRAF mutation enrolled on a phase I study of GSK1120212 + GSK118436, and experienced a near complete response lasting > 6 months; 1 with a PIK3CA mutation was enrolled on a phase I study of a PI3 kinase inhibitor; and 1 with HER2 amplification received trastuzumab with adjuvant chemoradiotherapy. Given the cohort size, statistical analysis was limited, with no significant correlations being found between genotype and pathologic features or survival. Conclusions: SNaPshot genetic profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad genetic profiling to expedite the identification of effective targeted therapies for patients with rare malignancies.