TP53 mutation spectrum in smokers and never smoking lung cancer patients
AbstractBackground: TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different...
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2016-05-01
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doaj-07cc48300421472889799803c163b7cd2020-11-24T22:48:13ZengFrontiers Media S.A.Frontiers in Genetics1664-80212016-05-01710.3389/fgene.2016.00085195636TP53 mutation spectrum in smokers and never smoking lung cancer patientsAnn Rita Halvorsen0Laxmi eSilwal-Pandit1Leonardo A Meza-Zepeda2Leonardo A Meza-Zepeda3Daniel eVodak4Phuong eVu5Camilla eSagerup6Eivind eHovig7Eivind eHovig8Eivind eHovig9Ola eMyklbost10Anne-Lise eBørresen-Dale11Anne-Lise eBørresen-Dale12Odd Terje Brustugun13Odd Terje Brustugun14Åslaug eHelland15Åslaug eHelland16Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayDepartment of Tumour Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayGenomics Core Facility, Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital, NorwayDepartment of Tumour Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayDepartment of Tumour Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Informatics, University of Oslo, Oslo, NorwayInstitute of Cancer Genetics and Informatics, Oslo University Hospital, Oslo, NorwayDepartment of Tumour Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayInstitute for Clinical Medicine, Faculty of Medicine, University of Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, NorwayAbstractBackground: TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different histological subtypes of lung cancer.Methods: We analysed tumour tissue from 394 non-small cell carcinomas including adenocarcinomas (n=229), squamous cell carcinomas (n=112), large cell carcinomas (n=30) and others (n=23) for mutations in TP53 by the use of Sanger sequencing (n=394) and next generation sequencing (n=100). Results: TP53 mutations were identified in 47.2% of the samples, with the highest frequency (65%) of mutations among squamous cell carcinomas. Among never-smokers, 36% carried a TP53 mutation, identified as a significant independent negative prognostic factor in this subgroup. For large cell carcinomas, a significantly prolonged progression free survival was found for those carrying a TP53 mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3%) compared to adenocarcinomas (9.1%).Conclusion: TP53 mutation patterns differ between the histological subgroups of lung cancers, as also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced TP53 mutations may have a different biological impact than TP53 mutations occurring in never-smokers.http://journal.frontiersin.org/Journal/10.3389/fgene.2016.00085/fulllung cancerTP53Mutation spectrumSquamous cell carcinomasNever smokersAdenocarcinomas |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ann Rita Halvorsen Laxmi eSilwal-Pandit Leonardo A Meza-Zepeda Leonardo A Meza-Zepeda Daniel eVodak Phuong eVu Camilla eSagerup Eivind eHovig Eivind eHovig Eivind eHovig Ola eMyklbost Anne-Lise eBørresen-Dale Anne-Lise eBørresen-Dale Odd Terje Brustugun Odd Terje Brustugun Åslaug eHelland Åslaug eHelland |
spellingShingle |
Ann Rita Halvorsen Laxmi eSilwal-Pandit Leonardo A Meza-Zepeda Leonardo A Meza-Zepeda Daniel eVodak Phuong eVu Camilla eSagerup Eivind eHovig Eivind eHovig Eivind eHovig Ola eMyklbost Anne-Lise eBørresen-Dale Anne-Lise eBørresen-Dale Odd Terje Brustugun Odd Terje Brustugun Åslaug eHelland Åslaug eHelland TP53 mutation spectrum in smokers and never smoking lung cancer patients Frontiers in Genetics lung cancer TP53 Mutation spectrum Squamous cell carcinomas Never smokers Adenocarcinomas |
author_facet |
Ann Rita Halvorsen Laxmi eSilwal-Pandit Leonardo A Meza-Zepeda Leonardo A Meza-Zepeda Daniel eVodak Phuong eVu Camilla eSagerup Eivind eHovig Eivind eHovig Eivind eHovig Ola eMyklbost Anne-Lise eBørresen-Dale Anne-Lise eBørresen-Dale Odd Terje Brustugun Odd Terje Brustugun Åslaug eHelland Åslaug eHelland |
author_sort |
Ann Rita Halvorsen |
title |
TP53 mutation spectrum in smokers and never smoking lung cancer patients |
title_short |
TP53 mutation spectrum in smokers and never smoking lung cancer patients |
title_full |
TP53 mutation spectrum in smokers and never smoking lung cancer patients |
title_fullStr |
TP53 mutation spectrum in smokers and never smoking lung cancer patients |
title_full_unstemmed |
TP53 mutation spectrum in smokers and never smoking lung cancer patients |
title_sort |
tp53 mutation spectrum in smokers and never smoking lung cancer patients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2016-05-01 |
description |
AbstractBackground: TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different histological subtypes of lung cancer.Methods: We analysed tumour tissue from 394 non-small cell carcinomas including adenocarcinomas (n=229), squamous cell carcinomas (n=112), large cell carcinomas (n=30) and others (n=23) for mutations in TP53 by the use of Sanger sequencing (n=394) and next generation sequencing (n=100). Results: TP53 mutations were identified in 47.2% of the samples, with the highest frequency (65%) of mutations among squamous cell carcinomas. Among never-smokers, 36% carried a TP53 mutation, identified as a significant independent negative prognostic factor in this subgroup. For large cell carcinomas, a significantly prolonged progression free survival was found for those carrying a TP53 mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3%) compared to adenocarcinomas (9.1%).Conclusion: TP53 mutation patterns differ between the histological subgroups of lung cancers, as also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced TP53 mutations may have a different biological impact than TP53 mutations occurring in never-smokers. |
topic |
lung cancer TP53 Mutation spectrum Squamous cell carcinomas Never smokers Adenocarcinomas |
url |
http://journal.frontiersin.org/Journal/10.3389/fgene.2016.00085/full |
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