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D. Wu
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MINI 13 - Genetic Alterations and Testing (ID 120)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:Y. Koh, R.K. Thomas
- Coordinates: 9/08/2015, 10:45 - 12:15, 205+207
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MINI13.04 - Characterization of Gene Mutations and Copy Number Alterations in Chinese Squamous Cell Lung Carcinomas (ID 3110)
10:45 - 12:15 | Author(s): D. Wu
- Abstract
- Presentation
Background:
Identification of driver mutations has led to the dramatic improvement in personalized therapy for lung adenocarcinoma. However, few targeted therapeutics are approved for treatment of squamous cell lung carcinoma. The identification of druggable molecular targets in SqCLC has been becoming a top research priority. Therefore, the aim of this study was to analyze the driver mutation profiles in a large cohort of Chinese squamous cell lung carcinomas to identify potential therapeutic targets.
Methods:
Approximately 2,800 COSMIC mutations from 50 oncogenes and tumor suppressor genes were analyzed on 159 samples by using Ion Torrent semiconductor-based next-generation sequencing. The gene copy numbers of FGFR1, EGFR, HER2, PDGFRA, CCND1, SOX2, CDKN2A, and PTEN were assessed by FISH on 250 samples. In addition, the status of PTEN expression was examined by immunohistochemistry on 250 samples.
Results:
Somatic mutations were detected in 73.6% (117/159) of patients. The most commonly mutated gene detected in this study was TP53 (56.0%, 89/159), followed by CDKN2A (8.8%, 14/159), PI3KCA (8.8%, 14/159), KRAS (4.4%, 7/159), EGFR (3.1%, 5/159), FBXW7 (2.5%, 4/159), PTEN (2.5%, 4/159), FGFR3 (1.3%, 2/159), AKT1 (1.3%, 2/159) and KIT (0.6%, 1/159). Copy number alterations were present in 77.6% (191/246) of patients, including FGFR1 amplification (13.7%, 34/248), EGFR amplification (11.4%, 28/246), HER2 amplification (8.9%, 22/246), PDGFRA amplification (7.7%, 19/246), CCND1 amplification (11.0%, 27/246), SOX2 amplification (35.0%, 86/246), CDKN2A deletion (18.7%, 46/246), and PTEN deletion (29.3%, 72/246). The loss of PTEN expression was observed in 43.5% (108/248) of patients. TP53 mutations were significantly more common in men and smokers, while the frequency of EGFR mutation was significantly higher in women and never smokers. Amplification of FGFR1, CCND1 and SOX2 genes were significantly associated with smoking. The incidence of FGFR1 amplification in patients without lymph node metastasis was significantly higher than that in patients with lymph node metastasis (19.4% vs. 10.2%，P=0.043). The frequency of SOX2 amplification in tumors with moderate and poor differentiation was significantly higher than that in tumors with well differentiation (39.6% vs. 33.6% vs. 0%，P=0.036). The incidence of loss of PTEN protein expression in patients with pleural invasion was 51.2%, which was significantly higher than that in patients without pleural invasion (P=0.017). The loss of PTEN expression was significantly associated with PTEN gene deletion (P=0.001). No significant association was observed between the molecular abnormalities and disease-free survival and overall survival.
Conclusion:
Genetic alterations are common in squamous cell lung cancers. The findings of this study may facilitate the identification of molecular target candidates for precision medicine in patients with squamous cell lung cancers.
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