Salivary Duct Carcinoma: Actionable Somatic Mutations Identified by Massively Parallel Sequencing
Snjezana Dogan, Nora Katabi, Roman Yelensky, Kai Wang, Phil Stephens, Michael F Berger. Memorial Sloan-Kettering Cancer Center, New York, NY; Foundation Medicine Inc., Cambridge, MA
Background: Salivary duct carcinoma (SDC) is a highly aggressive malignant epithelial tumor that comprises about 9% of salivary gland malignancies arising most frequently in the parotid. Most SDC patients present with locally advanced disease, and currently the prognosis is poor with a median survival of 3 years. A comprehensive mutational profiling of SDC is necessary in order to identify actionable genetic alterations and to potentially expand the range of treatment options for SDC patients.
Design: Ten primary surgically resected SDC cases were selected for targeted DNA sequencing of 189 cancer-related genes. Upon the histological review, 40 um of formalin-fixed paraffin embedded (FFPE) tumor and the matching normal tissue sample (available in 8 cases) were subjected for DNA extraction followed by sequencing library construction and hybridization-based capture of 3230 exons and 37 intronic intervals. Deep sequencing was performed, yielding an average coverage of >750X for uniquely-mapping reads. Sequence data were analyzed for single nucleotide variants, small insertions and deletions, fusion genes and amplifications.
Results: Eight of ten (80%) of SDC harbor actionable somatic mutations and/or amplifications including 4 PIK3CA mutations (40%), 1 BRAF V600E mutation (10%), and 3 cases with ERRB2 amplifications (30%), one of which also harbors ERBB2 S310F activating mutation. In three cases, putative loss-of-function mutations were detected in NF1 gene. Additional study cases are pending deep sequencing.
Conclusions: The majority of SDC cases harbor mutations potentially targetable with currently established therapies. Massively parallel sequencing of a large panel of cancer-related genes is a powerful method for detection of actionable genetic alterations and could be used to select SDC patients eligible for clinical trials. Almost one third of SDC have potentially significant genetic alterations in NF1 tumor suppressor gene, and further studies are necessary to elucidate the role of NF1 in the pathogenesis of SDC.
Category: Head & Neck
Monday, March 4, 2013 2:15 PM
Proffered Papers: Section F, Monday Afternoon