title: PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheffler
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Bos
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Masyar
authors.initials: M
authors.lastname: Gardizi
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: König
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michels
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Fassunke
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Heydt
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Künstlinger
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Ihle
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Ueckeroth
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Albus
authors.affiliation: Department for Pulmonology and Thoracic Oncology, Lung Clinic Hemer, Hemer, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Serke
authors.affiliation: Clinic for Hematology, Oncology and Palliative Care, Malteser Hospital, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gerigk
authors.affiliation: Clinic for Hematology, Oncology and Palliative Care, Malteser Hospital, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schulte
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Töpelt
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Nogova
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Gastrointestinal Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.affiliation: Lung Clinic Merheim, Hospital of Cologne, Cologne, Germany.
authors.forename: Walburga
authors.initials: W
authors.lastname: Engel-Riedel
authors.affiliation: Lung Clinic Merheim, Hospital of Cologne, Cologne, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Stoelben
authors.affiliation: Johanniter Hospital, Evangelical Clinics of Bonn, Bonn, Germany.
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.affiliation: Clinic for Pneumology and Allergology Center for Sleep Medicine and Respiratory Care, Bethanien Hospital, Solingen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Randerath
authors.affiliation: Clinic for Pneumology and Allergology Center for Sleep Medicine and Respiratory Care, Bethanien Hospital, Solingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Kaminsky
authors.affiliation: Department of Medicine IV, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.affiliation: Department of Medicine IV, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Becker
authors.affiliation: Institute of Medical Statistics, Informatics, and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany.Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human