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Updated: Apr 18, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
High Discrepancy of Driver Mutations in Patients with NSCLC and Synchronous Multiple Lung Ground-Glass Nodules
Chunyan Wu1, Chao Zhao2, Yang Yang3
1Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
Background:
The aim of this study was to investigate the discordance rates of eight known driver mutations among multiple matched intrapulmonary ground-glass nodules (GGNs) in non-small-cell lung cancer (NSCLC) patients.
Methods:
Tumors from 35 patients with multiple lesions resected, including confirmed NSCLC and at least one GGN, were analyzed for mutations in EGFR, KRAS, HER2, BRAF, and PIK3CA together with fusions in ALK, ROS1, and RET.
Results:
From 35 patients, a total of 72 lesions (60 were GGNs) were analyzed. These included nine adenocarcinoma in situ, nine minimal invasive adenocarcinoma, and 54 invasive adenocarcinoma. Among them, 33 tumor lesions (45.8 %) were found harboring EGFR mutations: 13 tumors with exon 19 deletion, 18 with L858R on exon 21, and two with both exon 19 del and L858R mutation. There were 5 tumors (6.9 %) harboring EML4-ALK fusion, four HER2 mutations (5.6%), three KRAS mutations (4.2%), one ROS1 fusion and one BRAF mutation. When we used the matched tumors to determine the intertumor discrepancy, only six out of 30 patients harbored identical mutations. The discordance rate of driver mutations was 80% (24 of 30) in those patients harboring at least one of the detected driver mutations. The median disease-free survival was 41.2 months (95% confidence interval: 35.8-52.6 months) and the median overall survival was "still not reached" in this cohort.
Conclusions:
We found a high discrepancy of driver mutations among NSCLC patients with GGNs and a favorable prognosis after multiple lesions resection, which support surgical resection in this situation as a reasonable approach.
Insights
High rates of driver mutation discordance were found in non-small-cell lung cancer (NSCLC) patients with multiple ground-glass nodules (GGNs). Surgical resection of these lesions is a reasonable approach, offering a favorable prognosis.
Area of Science:
- Oncology
- Genetics
- Thoracic Surgery
Background:
- Non-small-cell lung cancer (NSCLC) often presents with multiple intrapulmonary ground-glass nodules (GGNs).
- Understanding driver mutation profiles in these multifocal lesions is crucial for treatment decisions.
Purpose of the Study:
- To investigate the discordance rates of known driver mutations across multiple GGNs in NSCLC patients.
- To evaluate the prognostic implications of these mutations and surgical resection.
Main Methods:
- Analysis of driver mutations (EGFR, KRAS, HER2, BRAF, PIK3CA) and fusions (ALK, ROS1, RET) in 72 lesions from 35 NSCLC patients.
- Comparison of mutation profiles between matched intrapulmonary lesions to determine discordance rates.
Main Results:
- A high discordance rate of 80% for driver mutations was observed among patients with multiple lesions.
- EGFR mutations were the most common (45.8%), followed by ALK fusions (6.9%).
- Median disease-free survival was 41.2 months, with overall survival not yet reached.
Conclusions:
- Significant driver mutation discrepancies exist among GGNs in NSCLC patients.
- Surgical resection of multiple GGNs in NSCLC is supported by a favorable prognosis.
- This finding supports surgical intervention as a viable strategy for managing multifocal NSCLC with GGNs.
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