| The Introduction of Systematic Genomic Testing for Patients with Non-Small-Cell Lung Cancer. | |
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MedLine Citation:
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PMID: 23154547 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND:: Genomic testing to identify driver mutations that enable targeted therapy is emerging for patients with non-small-cell lung cancer (NSCLC). We report the implementation of systematic prospective genotyping for somatic alterations in BRAF, PIK3CA, HER2, and ALK, in addition to EGFR and KRAS, in NSCLC patients at the Dana-Farber Cancer Institute. METHODS:: Patients with NSCLC were prospectively referred by their providers for clinical genotyping. Formalin-fixed, paraffin embedded tumor samples were analyzed by Sanger sequencing for mutations in selected exons of EGFR, KRAS, BRAF, PIK3CA, and HER2. ALK rearrangements were detected by fluorescence in situ hybridization or immunohistochemistry. RESULTS:: Between July 1, 2009 and August 1, 2010, 427 specimens from 419 patients were referred for genomic characterization; 344 (81%) specimens were successfully genotyped with a median turnaround time of 31 days (range, 9-155). Of the 344 specimens, 185 (54%) had at least one identifiable somatic alteration (KRAS: 24%, EGFR: 17%, ALK: 5%, BRAF: 5%, HER2: 4%, PIK3CA: 2%). As of August 1, 2011, 63 of 288 advanced NSCLC patients (22%) had received molecularly targeted therapy based on their genotypic results, including 34 of 42 patients (81%) with EGFR mutations, 12 of 15 (80%) with ALK rearrangements, and 17 of 95 (18%) with KRAS, BRAF, or HER2 mutations. CONCLUSIONS:: Large-scale testing for somatic alterations in EGFR, KRAS, BRAF, PIK3CA, HER2, and ALK is feasible and impacts therapeutic decisions. As the repertoire for personalized therapies expands in lung cancer and other malignancies, there is a need to develop new genomics technologies that can generate a comprehensive genetic profile of tumor specimens in a time- and cost-effective manner. |
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Authors:
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Stephanie Cardarella; Taylor M Ortiz; Victoria A Joshi; Mohit Butaney; David M Jackman; David J Kwiatkowski; Beow Y Yeap; Pasi A Jänne; Neal I Lindeman; Bruce E Johnson |
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Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Volume: 7 ISSN: 1556-1380 ISO Abbreviation: J Thorac Oncol Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101274235 Medline TA: J Thorac Oncol Country: - |
Other Details:
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Languages: ENG Pagination: 1767-1774 Citation Subset: - |
Affiliation:
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*Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; †Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; ‡Department of Medicine, Harvard Medical School, Boston, Massachusetts; §Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, Massachusetts; Departments of ‖Pathology and ¶Medicine, Massachusetts General Hospital, Boston, Massachusetts; #The Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts; **Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; and ††Department of Pathology, Harvard Medical School, Boston, Massachusetts. |
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