PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies
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// Matthias Scheffler 1,2,* , Marc Bos 1,2,* , Masyar Gardizi 1,2,* , Katharina König 1,3,* , Sebastian Michels 1,2 , Jana Fassunke 1,3 , Carina Heydt 1,3 , Helen Künstlinger 1,3 , Michaela Ihle 1,3 , Frank Ueckeroth 1,3 , Kerstin Albus 1,3 , Monika Serke 4 , Ulrich Gerigk 5 , Wolfgang Schulte 5 , Karin Töpelt 1,2 , Lucia Nogova 1,2 , Thomas Zander 1,6 , Walburga Engel-Riedel 7 , Erich Stoelben 7 , Yon-Dschun Ko 8 , Winfried Randerath 9 , Britta Kaminsky 9 , Jens Panse 10 , Carolin Becker 10 , Martin Hellmich 11 , Sabine Merkelbach-Bruse 1,3 , Lukas C. Heukamp 1,3,* , Reinhard Büttner 1,3,* and Jürgen Wolf 1,2,* 1 Center for Integrated Oncology Köln Bonn, Cologne, Germany 2 Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany 3 Institute of Pathology, University Hospital of Cologne, Cologne, Germany 4 Department for Pulmonology and Thoracic Oncology, Lung Clinic Hemer, Hemer, Germany 5 Clinic for Hematology, Oncology and Palliative Care, Malteser Hospital, Bonn, Germany 6 Gastrointestinal Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany 7 Lung Clinic Merheim, Hospital of Cologne, Cologne, Germany 8 Johanniter Hospital, Evangelical Clinics of Bonn, Bonn, Germany 9 Clinic for Pneumology and Allergology Center for Sleep Medicine and Respiratory Care, Bethanien Hospital, Solingen, Germany 10 Department of Medicine IV, University Hospital RWTH Aachen, Aachen, Germany 11 Institute of Medical Statistics, Informatics, and Epidemiology, University of Cologne, Cologne, Germany * These authors contributed equally to this work Correspondence: Jürgen Wolf, email: // Keywords : Non-small cell lung cancer, PIK3CA, mutation, lung cancer, PI3K Received : October 22, 2014 Accepted : November 25, 2014 Published : November 26, 2014 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.
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There is growing evidence that KRAS-mutated lung cancer does not represent a homogeneous NSCLC subgroup.
“According to recent molecular findings, there is growing evidence that KRASmutated lung cancer does not represent a homogeneous NSCLC subgroup.15,22,39,40”
From K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways (2019) · cites this paper as [40]
With the exception of PI3KCA mutations, the majority of oncogenic drivers in NSCLC are usually mutually exclusive, including EGFR mutations.
“With the exception of PI3KCA mutations [13], the majority of oncogenic drivers in NSCLC are usually mutually exclusive, including EGFR mutations.”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [13]
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- Authors
- Scheffler, M., Bos, M., Gardizi, M., König, K., Michels, S., Fassunke, J., Heydt, C., Künstlinger, H., Ihle, M., Ueckeroth, F., Albus, K., Serke, M., Gerigk, U., Schulte, W., Töpelt, K., Nogova, L., Zander, T., Engel-Riedel, W., Stoelben, E., Ko, Y.-D., Randerath, W., Kaminsky, B., Panse, J., Becker, C., Hellmich, M., Merkelbach-Bruse, S., Heukamp, L. C., Büttner, R., & Wolf, J.
- Affiliations
- University Hospital Cologne (DE)
- Lungenklinik Hemer (DE)
- Clinic for Hematology, Oncology and Palliative Care, Malteser Hospital, Bonn, Germany
- Center for Integrated Oncology Köln Bonn, Cologne, Germany
- Lungenklinik Köln-Merheim (DE)
- Johanniter-Krankenhaus Bonn (DE)
- Krankenhaus Bethanien (DE)
- Universitätsklinikum Aachen (DE)
- University of Cologne (DE)
- Corresponding author
- Scheffler, Matthias
- Bos, Marc
- Gardizi, Masyar
- Heukamp, Lukas C.
- ORCID
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2014-11-26
- Volume
- 6
- Issue
- 2
- Pages
- 1315-1326
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4359235
- OpenAlex
- W2120111652
- Cited by
- 147
- References
- 28
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 17 · 2023: 22 · 2022: 9 · 2021: 16 · 2020: 15 · 2019: 13 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 5
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- PIK3CA mutation, non-small cell lung cancer, genetic heterogeneity, prognostic impact, prior malignancy, second primary malignancy, prognostic factors
- MeSH terms
- Adenocarcinoma, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Exons, Female, Gene Frequency, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Prognosis, Cohort Studies, Survival Analysis, Neoplasms, Second Primary, Genetic Heterogeneity, Phosphatidylinositol 3-Kinases, Class I Phosphatidylinositol 3-Kinases, High-Throughput Nucleotide Sequencing
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