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Updated: Jun 20, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Amplification of chromosomal segment 4q12 in non-small cell lung cancer
Alex H Ramos1, Amit Dutt, Craig Mermel
1Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract:
In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCLC). Single nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFRalpha activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFRalpha/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFRalpha/KIT inhibitors.
Insights
Recurrent amplifications of PDGFRA and KIT genes in chromosome 4q12 are found in non-small cell lung cancer (NSCLC). These findings suggest PDGFRA and KIT may act as oncogenes, potentially responding to targeted therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Proto-oncogenes are frequently altered by genomic amplification in cancer.
- The 4q12 chromosomal segment harbors proto-oncogenes PDGFRA and KIT.
Purpose of the Study:
- To investigate focal amplifications of the 4q12 segment in non-small cell lung cancer (NSCLC).
- To explore the role of PDGFRA and KIT in NSCLC development and identify potential therapeutic targets.
Main Methods:
- Single nucleotide polymorphism (SNP) array analysis.
- Fluorescent in situ hybridization (FISH).
- Cell line experiments using shRNAs and small molecule inhibitors (imatinib, sunitinib).
Main Results:
- Recurrent focal amplifications of 4q12, overlapping PDGFRA and KIT, were identified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas.
- The NSCLC cell line NCI-H1703 showed focal PDGFRA amplification and dependency on PDGFRalpha activity for growth.
- Inhibition of PDGFRalpha or KIT activity in NCI-H1703 cells led to growth inhibition.
Conclusions:
- PDGFRA and KIT are implicated as potential oncogenes in NSCLC.
- Targeted inhibition of PDGFRalpha/KIT shows promise, but further research is needed to define responsive tumor characteristics.
