Effective Assessment of egfr Mutation Status in Bronchoalveolar Lavage and Pleural Fluids by Next-Generation Sequencing
| Autor: | Maela Del Grammastro, Patrizia Viola, Sandra Rosini, Lara Felicioni, Franco Cuccurullo, Alessia Di Lorito, Tommaso D'Antuono, Antonio Marchetti, Giampaolo Filice, Fiamma Buttitta, Irene Centi, Sara Malatesta, Roberta Zappacosta |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Pathology Lung Neoplasms DNA Mutational Analysis Adenocarcinoma of Lung Adenocarcinoma DNA sequencing symbols.namesake Cytology Internal medicine Humans Medicine Sanger sequencing Lung medicine.diagnostic_test business.industry High-Throughput Nucleotide Sequencing Cancer Exons medicine.disease Pleural Effusion Malignant ErbB Receptors Bronchoalveolar lavage medicine.anatomical_structure Egfr mutation Mutation symbols business Bronchoalveolar Lavage Fluid |
| Zdroj: | Clinical Cancer Research. 19:691-698 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-12-1958 |
| Popis: | Purpose: The therapeutic choice for patients with lung adenocarcinoma depends on the presence of EGF receptor (EGFR) mutations. In many cases, only cytologic samples are available for molecular diagnosis. Bronchoalveolar lavage (BAL) and pleural fluid, which represent a considerable proportion of cytologic specimens, cannot always be used for molecular testing because of low rate of tumor cells. Experimental Design: We tested the feasibility of EGFR mutation analysis on BAL and pleural fluid samples by next-generation sequencing (NGS), an innovative and extremely sensitive platform. The study was devised to extend the EGFR test to those patients who could not get it due to the paucity of biologic material. A series of 830 lung cytology specimens was used to select 48 samples (BAL and pleural fluid) from patients with EGFR mutations in resected tumors. These samples included 36 cases with 0.3% to 9% of neoplastic cells (series A) and 12 cases without evidence of tumor (series B). All samples were analyzed by Sanger sequencing and NGS on 454 Roche platform. A mean of 21,130 ± 2,370 sequences per sample were obtained by NGS. Results: In series A, EGFR mutations were detected in 16% of cases by Sanger sequencing and in 81% of cases by NGS. Seventy-seven percent of cases found to be negative by Sanger sequencing showed mutations by NGS. In series B, all samples were negative for EGFR mutation by Sanger sequencing whereas 42% of them were positive by NGS. Conclusions: The very sensitive EGFR-NGS assay may open up to the possibility of specific treatments for patients otherwise doomed to re-biopsies or nontargeted therapies. Clin Cancer Res; 19(3); 691–8. ©2012 AACR. |
| Databáze: | OpenAIRE |
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