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Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR.
PLoS One. 2013; 8(11):e79820.Plos

Abstract

INTRODUCTION

Amplification of the fibroblast growth factor receptor 1 (FGFR1) gene has been described in tumors of non-small-cell lung cancer (NSCLC) patients. Prior reports showed conflicting rates of amplification frequency and clinical relevance.

MATERIALS AND METHODS

We developed a reliable real-time quantitative PCR assay to assess the frequency of FGFR1 amplification and assessed the optimal cutoff level of amplification for clinical application.

RESULTS

In a training cohort of 203 NSCLCs, we established that a 3.5-fold amplification optimally divided patients into groups with different survival rates with a clear threshold level. Those with FGFR1 amplification levels above 3.5-fold had an inferior survival. These data were confirmed in a validation cohort of 142 NSCLC. After adjusting for age, sex, performance status, stage, and histology, patients with FGFR1 amplification levels above 3.5 fold had a hazard ratio of 2.91 (95% CI- 1.14, 7.41; pvalue-0.025) for death in the validation cohort. The rates of FGFR1 amplification using the cutoff level of 3.5 were 5.1% in squamous cell and 4.1% in adenocarcinomas. There was a non-significant trend towards higher amplifications rates in heavy smokers (> 15 pack-years of cigarette consumption) as compared to light smokers.

DISCUSSION

Our data suggest that a 3.5-fold amplification of FGFR1 is of clinical importance in NSCLC. Our cutpoint analysis showed a clear threshold effect for the impact of FGFR1 amplification on patients' survival, which can be used as an initial guide for patient selection in trials assessing efficacy of novel FGFR inhibitors.

Authors+Show Affiliations

Karmanos Cancer Institute & Department of Oncology, Wayne State University, Detroit, Michigan, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

24255716

Citation

Gadgeel, Shirish M., et al. "Fibroblast Growth Factor Receptor 1 Amplification in Non-small Cell Lung Cancer By Quantitative Real-time PCR." PloS One, vol. 8, no. 11, 2013, pp. e79820.
Gadgeel SM, Chen W, Cote ML, et al. Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR. PLoS One. 2013;8(11):e79820.
Gadgeel, S. M., Chen, W., Cote, M. L., Bollig-Fischer, A., Land, S., Schwartz, A. G., & Bepler, G. (2013). Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR. PloS One, 8(11), e79820. https://doi.org/10.1371/journal.pone.0079820
Gadgeel SM, et al. Fibroblast Growth Factor Receptor 1 Amplification in Non-small Cell Lung Cancer By Quantitative Real-time PCR. PLoS One. 2013;8(11):e79820. PubMed PMID: 24255716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR. AU - Gadgeel,Shirish M, AU - Chen,Wei, AU - Cote,Michele L, AU - Bollig-Fischer,Aliccia, AU - Land,Susan, AU - Schwartz,Ann G, AU - Bepler,Gerold, Y1 - 2013/11/08/ PY - 2013/06/30/received PY - 2013/10/03/accepted PY - 2013/11/21/entrez PY - 2013/11/21/pubmed PY - 2014/7/26/medline SP - e79820 EP - e79820 JF - PloS one JO - PLoS One VL - 8 IS - 11 N2 - INTRODUCTION: Amplification of the fibroblast growth factor receptor 1 (FGFR1) gene has been described in tumors of non-small-cell lung cancer (NSCLC) patients. Prior reports showed conflicting rates of amplification frequency and clinical relevance. MATERIALS AND METHODS: We developed a reliable real-time quantitative PCR assay to assess the frequency of FGFR1 amplification and assessed the optimal cutoff level of amplification for clinical application. RESULTS: In a training cohort of 203 NSCLCs, we established that a 3.5-fold amplification optimally divided patients into groups with different survival rates with a clear threshold level. Those with FGFR1 amplification levels above 3.5-fold had an inferior survival. These data were confirmed in a validation cohort of 142 NSCLC. After adjusting for age, sex, performance status, stage, and histology, patients with FGFR1 amplification levels above 3.5 fold had a hazard ratio of 2.91 (95% CI- 1.14, 7.41; pvalue-0.025) for death in the validation cohort. The rates of FGFR1 amplification using the cutoff level of 3.5 were 5.1% in squamous cell and 4.1% in adenocarcinomas. There was a non-significant trend towards higher amplifications rates in heavy smokers (> 15 pack-years of cigarette consumption) as compared to light smokers. DISCUSSION: Our data suggest that a 3.5-fold amplification of FGFR1 is of clinical importance in NSCLC. Our cutpoint analysis showed a clear threshold effect for the impact of FGFR1 amplification on patients' survival, which can be used as an initial guide for patient selection in trials assessing efficacy of novel FGFR inhibitors. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24255716/Fibroblast_growth_factor_receptor_1_amplification_in_non_small_cell_lung_cancer_by_quantitative_real_time_PCR_ L2 - https://dx.plos.org/10.1371/journal.pone.0079820 DB - PRIME DP - Unbound Medicine ER -