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Jianping Wang
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P35 - Pathology - Genomics (ID 105)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P35.10 - Concomitant Driver Gene Mutations in Non-Small Cell Lung Cancer (ID 1488)
00:00 - 00:00 | Presenting Author(s): Jianping Wang
- Abstract
Introduction
The presence of co-occurring mutations in driver gene mutated lung cancer may confer distinct clinical features and limited response to TKIs targeted therapies. Of note, concomitant EGFR driver oncogenic events has been extensively investigated. However, studies of the concurrent mutational pattern of the driver genes other than EGFR were still limited.
Methods
Tissue samples from Chinese lung cancer patients were collected and underwent targeted next-generation sequencing (NGS) with more than 381 cancer related genes in the laboratory of 3D Medicines from January, 2017 to February, 2020.
Results
A total of 15,411 patients with lung cancer were included in the study. The molecular pattern of patients harboring ALK/ROS1/BRAF/MET sensitizing mutations were assessed. Amongst all, 200 patients (1.3%) harbored ALK fusion mutations, including 163 with single EML4-ALK fusion, 23 with concurrent EML4-ALK and other fusions, and 14 with other ALK fusion. Concurrent ALK fusion and EGFR mutations were observed in seven patients, including three with EGFR 19del, two with EGFR L858R, one with EGFR p.R831C germline variant, and one with EGFR p.N468S (three of them also have concomitant EGFR amplification). Besides, there are 25 lung cancer patients harboring ROS1 fusion mutation (0.16%), BRAF V600E (n=30, 0.19%), or MET 14 exon mutant (METex14, n=34, 0.22%). Co-occurring driver gene mutations were observed in seven (7.9%) of these patients, including one with contaminant ROS1 fusion mutation and EGFR L858R/gain, one with BRAF V600E with EGFR L858R, one with BRAF V600E and KRAS G12V/D, and four patients with METex14 along with EGFR sensitizing mutations.
The genes with the highest co-occurrence rate with the studied driver genes are TP53 (n=63, 31.5% for ALK fusion; 14/25, 56% for ROS1 fusion; 15/30, 50% for BRAF V600E; 19/34, 55.9% for METex14) and CDKN2A/2B/1B (n=28, 14% for ALK fusion, 7/25, 28% for ROS fusion, 4/30, 13.3% for BRAF V6003; 2/34, 5.9% for METex14). In addition, a relatively high concomitant rate of BRAF V600E with SETD1 (13/30, 43.3%) and METex14 with MDM2 amplification (9/34, 26.5%) were observed. Positive PD-L1 expression was detected in 67.9% (142/209) of the evaluable patients, including 24.9% with a strong PD-L1 expression (≥50%). No significant differences of the PD-L1 expression level were observed across patients with different driver gene mutations (p>0.05).
Conclusion
Our study has provided the co-occurring mutational patterns of the driver genes other than EGFR in lung cancer, which may provide insights into the future treatment strategy of lung cancer patients.
