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Detection of Known and Novel FGFR Fusions in Non–Small Cell Lung Cancer by Comprehensive Genomic Profiling
- Source :
- Journal of Thoracic Oncology. 14:54-62
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Introduction Activation of the fibroblast growth factor receptor (FGFR) family through fusion with various partners has been described in multiple cancer types, including NSCLC. FGFR inhibitors are currently being evaluated clinically for patients whose tumors harbor these fusions. Methods Hybrid capture–based comprehensive genomic profiling was performed on 26,054 consecutive formalin-fixed, paraffin-embedded specimens of NSCLC. Results FGFR fusions retaining the kinase domain were identified in 0.2% of NSCLC cases; they included 37 fibroblast growth factor receptor gene 3 (FGFR3)–transforming acidic coiled-coil containing protein 3 gene (TACC3) fusion–positive cases, two fibroblast growth factor receptor 2 (FGFR2)–shootin 1 gene (KIAA1598 [also known as SHTN1]) fusion–positive cases, one BCL2 associated athanogene 4 gene (BAG4)–fibroblast growth factor receptor 1 gene (FGFR1) fusion–positive case, and 12 novel FGFR1, FGFR2, FGFR3, and fibroblast growth factor receptor 4 gene (FGFR4) fusion–positive cases. Co-occurring EGFR or MNNG HOS Transforming gene (MET) alterations were observed in 8% of cases (four of 52), KRAS mutation was observed in three additional cases, and FGFR1 or FGFR3 amplification was observed in 10% of cases. The two patients with co-occurring EGFR mutations were previously treated with EGFR inhibitors. One patient with a novel FGFR2–leucine zipper transcription factor like 1 gene (LZTFL1) fusion had a partial response to the pan-FGFR inhibitor JNJ-42756493 and remained progression-free for 11 months. Conclusion FGFR fusions were detected by using comprehensive genomic profiling in 0.2% of NSCLCs; they occurred primarily in the absence of other known driver alterations, or in a subset of cases, as likely mechanisms of acquired resistance. One patient with a novel FGFR2 fusion had clinical benefit from an investigational FGFR inhibitor, suggesting that these alterations may predict response to targeted therapies.
- Subjects :
- Adult
Male
musculoskeletal diseases
0301 basic medicine
Pulmonary and Respiratory Medicine
Lung Neoplasms
Oncogene Proteins, Fusion
03 medical and health sciences
0302 clinical medicine
Growth factor receptor
Carcinoma, Non-Small-Cell Lung
medicine
Humans
Lung cancer
Transcription factor
Aged
EGFR inhibitors
Aged, 80 and over
Fibroblast growth factor receptor 2
business.industry
Fibroblast growth factor receptor 1
Genomics
Fibroblast growth factor receptor 4
Middle Aged
medicine.disease
Receptors, Fibroblast Growth Factor
030104 developmental biology
Oncology
Fibroblast growth factor receptor
030220 oncology & carcinogenesis
Cancer research
Female
business
Subjects
Details
- ISSN :
- 15560864
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Oncology
- Accession number :
- edsair.doi.dedup.....172880e51a4a8f51d1e6a95858ce5e7f