Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment
| Autor: | Daniel G. Deschler, Dejan Juric, Vanessa L. Scialabba, Peter M. Sadow, Lori J. Wirth, Valentina Nardi, Keith T. Flaherty, Johanna C. Bendell, Dave Zhao, Darrell R. Borger, Dora Dias-Santagata, Kristin Bergethon, Arjola K. Cosper, Rebecca S. Heist, Yi Li, Anthony J. Iafrate, Julie M. Batten, Donald P. Lawrence |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf Cancer Research Genotype Class I Phosphatidylinositol 3-Kinases Receptor ErbB-2 Antineoplastic Agents Bioinformatics Salivary duct carcinoma Phosphatidylinositol 3-Kinases Young Adult medicine Humans Patient treatment General hospital Protein Kinase Inhibitors Genotyping Aged Neoplasm Staging Aged 80 and over Salivary gland business.industry Gene Expression Profiling Medical record Gene Amplification Middle Aged Cytotoxic chemotherapy Salivary Gland Neoplasms medicine.disease Carcinoma Ductal medicine.anatomical_structure Oncology Mutation Cancer gene Female business |
| Zdroj: | Clinical Cancer Research. 19:480-490 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents. Experimental Design: We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed. Results: Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients. Conclusion: SNaPshot molecular 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-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies. Clin Cancer Res; 19(2); 480–90. ©2012 AACR. |
| Databáze: | OpenAIRE |
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