Abstract 3543
Background
Non-small cell lung cancer is a major killer world-wide. While some lung adenocarcinomas have mutations qualifying for targeted therapy, this is not the case for the squamous cell carcinomas (SqCC). TP53 mutations exist in around 85% of squamous cell carcinomas, but the mutations are difficult to target directly. We explore the biology of TP53 mutated SqCC and search for putative targets for therapy.
Methods
Patients undergoing surgery for squamous cell lung carcinoma from 2006 to 2015 were included in the study (n = 198). Tumours were analysed using Illumina SNP6 for copy number alterations and Agilent 60K arrays for gene expression. TP53 mutations were analysed by Sanger sequencing. For 140 patients both gene expression and copy number data were available.
Results
Frequency plots for tumours harbouring TP53 mutations and TP53 wild type tumours were generated separately identifying genomic regions with differential frequency of copy number alterations. TP53 mutations are more frequent in the previously published gene expression subtypes Classical and Primitive compared with Basal and Secretory, but this does not seem to affect survival. Amplifications are particularly frequent in the Classical subtype. Target gene search was performed, identifying 148 genes with amplification and over-expression in TP53 mutated tumours compared with wild type tumours. Several of these putative target genes are previously studied as putative targets of therapy. The majority of the putative target genes are located on the chromosomal arms 2p for samples of the Secretory subtype, 2q for samples of the Primitive subtype and on 12p and 17q for samples of the Classical subtype.
Conclusions
There are distinct copy number alterations and gene expression patterns in TP53 mutated squamous cell lung cancers that can be used to identify novel targets of therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Oslo University Hospital.
Funding
The Norwegian Cancer Society, South-Eastern Norway Regional Health Authority.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract