Title |
PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies
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Published in |
Oncotarget, November 2014
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DOI | 10.18632/oncotarget.2834 |
Pubmed ID | |
Authors |
Matthias Scheffler, Marc Bos, Masyar Gardizi, Katharina König, Sebastian Michels, Jana Fassunke, Carina Heydt, Helen Künstlinger, Michaela Ihle, Frank Ueckeroth, Kerstin Albus, Monika Serke, Ulrich Gerigk, Wolfgang Schulte, Karin Töpelt, Lucia Nogova, Thomas Zander, Walburga Engel-Riedel, Erich Stoelben, Yon-Dschun Ko, Winfried Randerath, Britta Kaminsky, Jens Panse, Carolin Becker, Martin Hellmich, Sabine Merkelbach-Bruse, Lukas C. Heukamp, Reinhard Büttner, Jürgen Wolf |
Abstract |
Background: Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically. Patients and methods: Tumor tissue collected consecutively from 1144 NSCLC patients within a molecular screening network between March 2010 and March 2012 was analyzed for PIK3CA mutations using dideoxy-sequencing and next-generation sequencing (NGS). Clinical, pathological, and genetic characteristics of PIK3CA-mutated patients are described and compared with a control group of PIK3CA-wildtype patients. Results: Among the total cohort of 1144 patients we identified 42 (3.7%) patients with PIK3CA mutations in exon 9 and exon 20. These mutations were found with a higher frequency in sqamous cell carcinoma (8.9%) compared to adenocarcinoma (2.9%, p<0.001). The most common PIK3CA mutation was exon 9 E545K. The majority of patients (57.1%) had additional oncogenic driver aberrations. With the exception of EGFR-mutated patients, non of the genetically defined subgroups in this cohort had a significantly better median overall survival. Further, PIK3CA-mutated patients had a significantly higher incidence of malignancy prior to lung cancer (p<0.001). Conclusion: PIK3CA-mutated NSCLC represents a clinically and genetically heterogeneous subgroup in adenocarcinomas as well as in squamous cell carcinomas with a higher prevalence of these mutations in sqamous cell carcinoma. PIK3CA mutations have no negative impact on survival after surgery or systemic therapy. However, PIK3CA mutated lung cancer frequently develops in patients with prior malignancies. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 127 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 26 | 20% |
Student > Bachelor | 17 | 13% |
Student > Master | 14 | 11% |
Student > Ph. D. Student | 12 | 9% |
Other | 9 | 7% |
Other | 14 | 11% |
Unknown | 35 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 30 | 24% |
Biochemistry, Genetics and Molecular Biology | 25 | 20% |
Agricultural and Biological Sciences | 17 | 13% |
Nursing and Health Professions | 3 | 2% |
Immunology and Microbiology | 2 | 2% |
Other | 6 | 5% |
Unknown | 44 | 35% |