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Updated: Sep 10, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
CDKN2A alternations in non-small cell lung cancer: An evaluation using next-generation sequencing
Xu Feng1, Heng Chang1, Yuyin Xu1
1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China.
Next-generation sequencing (NGS) shows high accuracy for CDKN2A deletion detection in lung cancer, but false positives can occur. Careful interpretation of NGS results is crucial, especially with intermediate copy number values.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Next-generation sequencing (NGS) is a high-throughput method for assessing CDKN2A status in cancer.
- Discrepancies between NGS and fluorescence in situ hybridization (FISH) for copy number variations (CNVs) are occasionally noted.
- FISH is considered the gold standard for detecting CNVs.
Purpose of the Study:
- To evaluate the accuracy of NGS in detecting CDKN2A deletions.
- To compare NGS-based CDKN2A deletion detection with FISH results.
- To identify factors contributing to discrepancies between NGS and FISH.
Main Methods:
- Retrospective analysis of 1118 non-small cell lung cancer (NSCLC) patients.
- CDKN2A copy number deletions identified by NGS in 56 patients.
- Validation of 51 cases using FISH.
Main Results:
- FISH confirmed CDKN2A deletion in 88.2% of cases initially identified by NGS.
- Of the confirmed deletions, 93.3% were homozygous and 6.7% were heterozygous.
- Discordant cases (11.8%) showed normal CDKN2A copy number by FISH but intermediate CN values by NGS, often with unstable baselines or haploidy.
Conclusions:
- NGS demonstrates high concordance with FISH for CDKN2A deletion detection.
- False positives can arise from intermediate CN values, low tumor purity, or unstable CNV baselines.
- Careful evaluation of these factors is essential for interpreting NGS-based CDKN2A CNV results in clinical practice.
