Oncotarget

Clinical Research Papers:

PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies

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 and Jürgen Wolf _

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Oncotarget. 2015; 6:1315-1326. https://doi.org/10.18632/oncotarget.2834

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Abstract

Matthias Scheffler1,2,*, Marc Bos1,2,*, Masyar Gardizi1,2,*, Katharina König1,3,*, Sebastian Michels1,2, Jana Fassunke1,3, Carina Heydt1,3, Helen Künstlinger1,3, Michaela Ihle1,3, Frank Ueckeroth1,3, Kerstin Albus1,3, Monika Serke4, Ulrich Gerigk5, Wolfgang Schulte5, Karin Töpelt1,2, Lucia Nogova1,2, Thomas Zander1,6, Walburga Engel-Riedel7, Erich Stoelben7, Yon-Dschun Ko8, Winfried Randerath9, Britta Kaminsky9, Jens Panse10, Carolin Becker10, Martin Hellmich11, Sabine Merkelbach-Bruse1,3, Lukas C. Heukamp1,3,*, Reinhard Büttner1,3,* and Jürgen Wolf1,2,*

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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