Abstract
Purpose
NSCLC is the most common type of lung cancers. The purpose of this study is to screen cancer-related mutations in early LUAD in China through NGS technology, determine their correlation with clinical characteristics and provide basis for treatment decisions.
Methods
In this study, we performed a 583 gene panel to detect the mutational spectrum of the tumors which were collected from 98 LUAD patients. The sequencing data and clinical characteristics were analyzed.
Results
Mutations were identified in 94.9% of patients. EGFR had the highest mutation frequency which was detected in 66% of the patients and was significantly associated with female gender and non-smoking history. Other genes with high mutation frequency were TP53 (37%), ERBB2 (24%), BCOR (22%), ZFHX3 (19%), BTG1 (17%), ATR (16%), WWTR1 (15%), etc. TP53 mutations were significantly associated with medium and low differentiation of tumors; BCOR and BLM mutations with gender; WWTR1 mutations with age; and ATR mutations with visceral pleura invasion were observed. 61% of the patients harbored at less one actionable alteration associated with FDA-recognized or investigational drugs.
Conclusion
Multiple mutations in LUAD patients in this study have not previously been reported in NSCLC. Moreover, mutations in driver genes including EGFR, TP53, BCOR, BLM, WWTR1, and ATR were significantly related to clinical features. The panel used in this study is an effective approach for molecular analysis and can be applied in personalized treatment decision-making and drug development.
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Acknowledgements
The authors thank the medical workers and researchers from the department of thoracic surgery, pathology and laboratory of Peking Union Medical College Hospital for their excellent work in data collection, sequencing and analysis for this study.
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Supplementary Figure 1.
High frequency mutated genes are the driving genes of LUAD. A. Hot spot mutated sites in LUAD patients (N=98). B. Somatic interactions detected by using R. C. Plot showing tumor driver genes predicted based on positional clustering. The size of the point represents the number of clusters found in the gene. X-axis shows number of mutations in these clusters. (TIF 1333 kb)
Supplementary Figure 2.
The mutated sites of genes with high mutation frequency. (PDF 300 kb)
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Zhou, X., Xu, X., Tian, Z. et al. Mutational profiling of lung adenocarcinoma in China detected by next-generation sequencing. J Cancer Res Clin Oncol 146, 2277–2287 (2020). https://doi.org/10.1007/s00432-020-03284-w
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DOI: https://doi.org/10.1007/s00432-020-03284-w