Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon

PloS One
Claire RooneyElaine Kilgour

Abstract

FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1-3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90) were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1) in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analys...Continue Reading

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Oct 28, 2018·Nature Reviews. Clinical Oncology·Masaru Katoh
Dec 3, 2016·Chinese Medical Journal·Jian-Long MiaoShu-Hua Meng
May 7, 2020·Molecular Cancer Therapeutics·Gopika SenthilKumarAndrew M Baschnagel
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Nov 10, 2020·Life Sciences·Ioannis A Voutsadakis

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Methods Mentioned

BETA
Feature extraction
Assay
PCR
Genotyping
xenograft

Clinical Trials Mentioned

NCT01004224
NCT00979134

Software Mentioned

Cytogenomics Software
Nanostring
Feature extraction
CGH Analytics
SAS
R
Pipeline Pilot Tool ( NAPPA

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