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Open Access 01-12-2021 | NSCLC | Research

Whole genome copy number analyses reveal a highly aberrant genome in TP53 mutant lung adenocarcinoma tumors

Authors: Maria Moksnes Bjaanæs, Gro Nilsen, Ann Rita Halvorsen, Hege G. Russnes, Steinar Solberg, Lars Jørgensen, Odd Terje Brustugun, Ole Christian Lingjærde, Åslaug Helland

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Genetic alterations are common in non-small cell lung cancer (NSCLC), and DNA mutations and translocations are targets for therapy. Copy number aberrations occur frequently in NSCLC tumors and may influence gene expression and further alter signaling pathways. In this study we aimed to characterize the genomic architecture of NSCLC tumors and to identify genomic differences between tumors stratified by histology and mutation status. Furthermore, we sought to integrate DNA copy number data with mRNA expression to find genes with expression putatively regulated by copy number aberrations and the oncogenic pathways associated with these affected genes.

Methods

Copy number data were obtained from 190 resected early-stage NSCLC tumors and gene expression data were available from 113 of the adenocarcinomas. Clinical and histopathological data were known, and EGFR-, KRAS- and TP53 mutation status was determined. Allele-specific copy number profiles were calculated using ASCAT, and regional copy number aberration were subsequently obtained and analyzed jointly with the gene expression data.

Results

The NSCLC tumors tissue displayed overall complex DNA copy number profiles with numerous recurrent aberrations. Despite histological differences, tissue samples from squamous cell carcinomas and adenocarcinomas had remarkably similar copy number patterns. The TP53-mutated lung adenocarcinomas displayed a highly aberrant genome, with significantly altered copy number profiles including gains, losses and focal complex events. The EGFR-mutant lung adenocarcinomas had specific arm-wise aberrations particularly at chromosome7p and 9q. A large number of genes displayed correlation between copy number and expression level, and the PI(3)K-mTOR pathway was highly enriched for such genes.

Conclusions

The genomic architecture in NSCLC tumors is complex, and particularly TP53-mutated lung adenocarcinomas displayed highly aberrant copy number profiles. We suggest to always include TP53-mutation status when studying copy number aberrations in NSCLC tumors. Copy number may further impact gene expression and alter cellular signaling pathways.

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Title: Whole genome copy number analyses reveal a highly aberrant genome in TP53 mutant lung adenocarcinoma tumors
Authors: Maria Moksnes Bjaanæs
Gro Nilsen
Ann Rita Halvorsen
Hege G. Russnes
Steinar Solberg
Lars Jørgensen
Odd Terje Brustugun
Ole Christian Lingjærde
Åslaug Helland
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: NSCLC
Lung Cancer
Lung Cancer
NSCLC
Lung Cancer
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08811-7

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