Dataset Information

Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer.

ABSTRACT:

Background

Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma.

Methodology/principal findings

Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes-WHSC1L1, LETM2, and FGFR1-is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition.

Conclusions/significance

These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.

SUBMITTER: Dutt A

PROVIDER: S-EPMC3110189 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer.

Dutt Amit A Ramos Alex H AH Hammerman Peter S PS Mermel Craig C Cho Jeonghee J Sharifnia Tanaz T Chande Ajit A Tanaka Kumiko Elisa KE Stransky Nicolas N Greulich Heidi H Gray Nathanael S NS Meyerson Matthew M

PloS one 20110607 6

<h4>Background</h4>Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma.<h4>Methodology/principal findings</h4>Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes-WHSC1L1, LETM2, and FGFR1-is amplified in 3% of lung adenoca ...[more]

PMID: 21666749

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Project description:PurposeUsing standard-of-care CT images obtained from patients with a diagnosis of non-small cell lung cancer (NSCLC), we defined radiomics signatures predicting the sensitivity of tumors to nivolumab, docetaxel, and gefitinib.Experimental designData were collected prospectively and analyzed retrospectively across multicenter clinical trials [nivolumab, n = 92, CheckMate017 (NCT01642004), CheckMate063 (NCT01721759); docetaxel, n = 50, CheckMate017; gefitinib, n = 46, (NCT00588445)]. Patients were randomized to training or validation cohorts using either a 4:1 ratio (nivolumab: 72T:20V) or a 2:1 ratio (docetaxel: 32T:18V; gefitinib: 31T:15V) to ensure an adequate sample size in the validation set. Radiomics signatures were derived from quantitative analysis of early tumor changes from baseline to first on-treatment assessment. For each patient, 1,160 radiomics features were extracted from the largest measurable lung lesion. Tumors were classified as treatment sensitive or insensitive; reference standard was median progression-free survival (NCT01642004, NCT01721759) or surgery (NCT00588445). Machine learning was implemented to select up to four features to develop a radiomics signature in the training datasets and applied to each patient in the validation datasets to classify treatment sensitivity.ResultsThe radiomics signatures predicted treatment sensitivity in the validation dataset of each study group with AUC (95 confidence interval): nivolumab, 0.77 (0.55-1.00); docetaxel, 0.67 (0.37-0.96); and gefitinib, 0.82 (0.53-0.97). Using serial radiographic measurements, the magnitude of exponential increase in signature features deciphering tumor volume, invasion of tumor boundaries, or tumor spatial heterogeneity was associated with shorter overall survival.ConclusionsRadiomics signatures predicted tumor sensitivity to treatment in patients with NSCLC, offering an approach that could enhance clinical decision-making to continue systemic therapies and forecast overall survival.

Dataset Information

Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer.

Background

Methodology/principal findings

Conclusions/significance

Publications

Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer.

Similar Datasets

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