AUTHOR=Halvorsen Ann R. , Silwal-Pandit Laxmi , Meza-Zepeda Leonardo A. , Vodak Daniel , Vu Phuong , Sagerup Camilla , Hovig Eivind , Myklebost Ola , Børresen-Dale Anne-Lise , Brustugun Odd T. , Helland Åslaug 

TITLE=TP53 Mutation Spectrum in Smokers and Never Smoking Lung Cancer Patients

JOURNAL=Frontiers in Genetics

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2016.00085

DOI=10.3389/fgene.2016.00085

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold><italic>TP53</italic> 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 <italic>TP53</italic> mutations in never-smokers and in different histological subtypes of lung cancer.</p><p><bold>Methods:</bold> We analyzed tumor tissue from 394 non-small cell carcinomas including adenocarcinomas (<italic>n</italic> = 229), squamous cell carcinomas (<italic>n</italic> = 112), large cell carcinomas (<italic>n</italic> = 30), and others (<italic>n</italic> = 23) for mutations in <italic>TP53</italic> by the use of Sanger sequencing (<italic>n</italic> = 394) and next generation sequencing (<italic>n</italic> = 100).</p><p><bold>Results:</bold><italic>TP53</italic> 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 <italic>TP53</italic> 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 <italic>TP53</italic> mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3%) compared to adenocarcinomas (9.1%).</p><p><bold>Conclusion:</bold><italic>TP53</italic> mutation patterns differ between the histological subgroups of lung cancers, and are also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced <italic>TP53</italic> mutations may have a different biological impact than <italic>TP53</italic> mutations occurring in never-smokers.</p>