Document Detail


The introduction of systematic genomic testing for patients with non-small-cell lung cancer.
MedLine Citation:
PMID:  23154547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2012-11-16     Completed Date:  2013-05-07     Revised Date:  2013-12-06    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1767-74     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*,  pathology
Adult
Aged
Aged, 80 and over
Carcinoma, Large Cell / genetics*,  pathology
Carcinoma, Non-Small-Cell Lung / genetics*,  pathology
Carcinoma, Squamous Cell / genetics*,  pathology
Female
Genotype
Humans
In Situ Hybridization, Fluorescence
Lung Neoplasms / genetics*,  pathology
Male
Middle Aged
Mutation / genetics
Neoplasm Recurrence, Local / genetics*,  pathology
Neoplasm Staging
Prognosis
Prospective Studies
Tumor Markers, Biological / genetics*
Young Adult
Grant Support
ID/Acronym/Agency:
1RC2 CA148394-01/CA/NCI NIH HHS; 5R01-CA114465/CA/NCI NIH HHS; R01 CA114465/CA/NCI NIH HHS; RC2 CA148394/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological
Comments/Corrections

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