![]() Validated prognostic factors are limited to traditional clinical variables (overall stage, high grade, and poor differentiation), and no additional data on possible informative biomarkers is currently in clinical use. Patients usually present at an advanced stage, and have poor outcomes, with two-year overall survival rates as low as 25% in some cohorts. It is a rare tumor, with only a few hundred cases in the literature. Sinonasal Undifferentiated Carcinoma (SNUC) is a highly aggressive disease involving the anterior skull base, nasal cavity and paranasal sinuses. These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease. ![]() ConclusionĬollectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene ( PGAP3-SRPK1). We also validated a novel PGAP3- SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. Tobacco use was the only significant predictor of survival. Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/− CRT and CRT alone. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. We performed exome sequencing to characterize a series of SNUC tumors ( n = 5) and cell line (MDA8788–6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options.
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