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Updated: Apr 3, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Rare discrepancies in a driver gene alteration within histologically heterogeneous primary lung cancers
Wen-zhao Zhong1, Jian Su1, Fang-ping Xu2
1Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Objectives:
Most lung adenocarcinomas consist of mixtures of histological subtypes harboring different frequencies of driver gene mutations. However, little is known about intratumoral heterogeneity(ITH) within histologically heterogeneous primary lung cancers. Investigating key driver genes in respective morphological pattern is crucial to personalized treatment.
Methods:
Morphologically different areas within the same surgically resected adenocarcinomas were extracted from tissues to analyze gene status in each growth pattern. Driver genes, epidermal growth factor receptor (EGFR), KRAS and EML4-ALK, were assessed by assays with different sensitivities.
Results:
Seventy-nine consecutive eligible patients harboring a driver gene (EGFR=65; KRAS=10; EML4-ALK=4) were enrolled. For EGFR mutations, ITH occurred in 13.3% (8/60) by direct sequencing (DS) and 1.7% (1/60) by amplification refractory mutation system (ARMS) (P=0.016) among adenocarcinomas, but consistent within five adeno-squamous cell carcinomas by both methods. ITH among KRAS mutations were detected in 20% (2/10) by DS, whereas consistent (10/10) by high resolution melting. No discrepancies in EML4-ALK rearrangements existed according to fluorescence in situ hybridization.
Conclusion:
Rare ITHs of EGFR/KRAS/EML4-ALK alterations within histologically heterogeneous primary lung adenocarcinomas existed by methods with higher sensitivity. Discrepancies might be due to abundance of mutant tumor cells and detection assays.
