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Oncotarget. 2015 Jan 20;6(2):1315-26.

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

Author information

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.
12
Center for Integrated Oncology Köln Bonn, Cologne, Germany.Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.

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.

PMID:
25473901
PMCID:
PMC4359235
DOI:
10.18632/oncotarget.2834
[Indexed for MEDLINE]
Free PMC Article

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