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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...

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Autores principales: 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
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
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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.
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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
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