Universität zu Köln

Scheffler, Matthias ORCID: 0000-0002-9031-1368, Bos, Marc, Gardizi, Masyar, Koenig, Katharina, Michels, Sebastian, Fassunke, Jana, Heydt, Carina, Kuenstlinger, Helen, Ihle, Michaela, Ueckeroth, Frank, Albus, Kerstin, Serke, Monika, Gerigk, Ulrich, Schulte, Wolfgang, Toepelt, 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., Buettner, Reinhard and Wolf, Juergen (2015). PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies. Oncotarget, 6 (2). S. 1315 - 1327. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Scheffler, Matthias UNSPECIFIED orcid.org/0000-0002-9031-1368 UNSPECIFIED Bos, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Gardizi, Masyar UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Michels, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Fassunke, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuenstlinger, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Ihle, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Ueckeroth, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Albus, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Serke, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerigk, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulte, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Toepelt, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Nogova, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Engel-Riedel, Walburga UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoelben, Erich UNSPECIFIED UNSPECIFIED UNSPECIFIED Ko, Yon-Dschun UNSPECIFIED UNSPECIFIED UNSPECIFIED Randerath, Winfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaminsky, Britta UNSPECIFIED UNSPECIFIED UNSPECIFIED Panse, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmich, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-414567
DOI:	10.18632/oncotarget.2834
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	2
Page Range:	S. 1315 - 1327
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ONCOGENE MUTATIONS; PI3K PATHWAY; ADENOCARCINOMA; INHIBITORS; H1047R Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41456