Cargando…
PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies
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 collec...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359235/ https://www.ncbi.nlm.nih.gov/pubmed/25473901 |
_version_ | 1782361364270940160 |
---|---|
author | Scheffler, Matthias Bos, Marc Gardizi, Masyar König, Katharina Michels, Sebastian Fassunke, Jana Heydt, Carina Künstlinger, Helen Ihle, Michaela Ueckeroth, Frank Albus, Kerstin Serke, Monika Gerigk, Ulrich Schulte, Wolfgang Töpelt, Karin Nogova, Lucia Zander, Thomas Engel-Riedel, Walburga Stoelben, Erich Ko, Yon-Dschun Randerath, Winfried Kaminsky, Britta Panse, Jens Becker, Carolin Hellmich, Martin Merkelbach-Bruse, Sabine Heukamp, Lukas C. Büttner, Reinhard Wolf, Jürgen |
author_facet | Scheffler, Matthias Bos, Marc Gardizi, Masyar König, Katharina Michels, Sebastian Fassunke, Jana Heydt, Carina Künstlinger, Helen Ihle, Michaela Ueckeroth, Frank Albus, Kerstin Serke, Monika Gerigk, Ulrich Schulte, Wolfgang Töpelt, Karin Nogova, Lucia Zander, Thomas Engel-Riedel, Walburga Stoelben, Erich Ko, Yon-Dschun Randerath, Winfried Kaminsky, Britta Panse, Jens Becker, Carolin Hellmich, Martin Merkelbach-Bruse, Sabine Heukamp, Lukas C. Büttner, Reinhard Wolf, Jürgen |
author_sort | Scheffler, Matthias |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4359235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-43592352015-03-27 PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies Scheffler, Matthias Bos, Marc Gardizi, Masyar König, Katharina Michels, Sebastian Fassunke, Jana Heydt, Carina Künstlinger, Helen Ihle, Michaela Ueckeroth, Frank Albus, Kerstin Serke, Monika Gerigk, Ulrich Schulte, Wolfgang Töpelt, Karin Nogova, Lucia Zander, Thomas Engel-Riedel, Walburga Stoelben, Erich Ko, Yon-Dschun Randerath, Winfried Kaminsky, Britta Panse, Jens Becker, Carolin Hellmich, Martin Merkelbach-Bruse, Sabine Heukamp, Lukas C. Büttner, Reinhard Wolf, Jürgen Oncotarget Clinical Research Paper 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. Impact Journals LLC 2014-11-26 /pmc/articles/PMC4359235/ /pubmed/25473901 Text en Copyright: © 2015 Scheffler et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Clinical Research Paper Scheffler, Matthias Bos, Marc Gardizi, Masyar König, Katharina Michels, Sebastian Fassunke, Jana Heydt, Carina Künstlinger, Helen Ihle, Michaela Ueckeroth, Frank Albus, Kerstin Serke, Monika Gerigk, Ulrich Schulte, Wolfgang Töpelt, Karin Nogova, Lucia Zander, Thomas Engel-Riedel, Walburga Stoelben, Erich Ko, Yon-Dschun Randerath, Winfried Kaminsky, Britta Panse, Jens Becker, Carolin Hellmich, Martin Merkelbach-Bruse, Sabine Heukamp, Lukas C. Büttner, Reinhard Wolf, Jürgen PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies |
title | PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies |
title_full | PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies |
title_fullStr | PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies |
title_full_unstemmed | PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies |
title_short | PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies |
title_sort | pik3ca mutations in non-small cell lung cancer (nsclc): genetic heterogeneity, prognostic impact and incidence of prior malignancies |
topic | Clinical Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359235/ https://www.ncbi.nlm.nih.gov/pubmed/25473901 |
work_keys_str_mv | AT schefflermatthias pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT bosmarc pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT gardizimasyar pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT konigkatharina pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT michelssebastian pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT fassunkejana pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT heydtcarina pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT kunstlingerhelen pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT ihlemichaela pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT ueckerothfrank pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT albuskerstin pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT serkemonika pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT gerigkulrich pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT schultewolfgang pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT topeltkarin pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT nogovalucia pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT zanderthomas pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT engelriedelwalburga pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT stoelbenerich pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT koyondschun pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT randerathwinfried pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT kaminskybritta pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT pansejens pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT beckercarolin pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT hellmichmartin pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT merkelbachbrusesabine pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT heukamplukasc pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT buttnerreinhard pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies AT wolfjurgen pik3camutationsinnonsmallcelllungcancernsclcgeneticheterogeneityprognosticimpactandincidenceofpriormalignancies |