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
5544 - Evaluation of a radiomic signature of CD8 cells in patients treated with immunotherapy-radiotherapy in three clinical trials.
Presenter: Roger Sun
Session: Poster Display session 3
Resources:
Abstract
1117 - Biomarkers predictive of overall survival in advanced cancer patients treated with a peptide-based cancer vaccine.
Presenter: Shigetaka Suekane
Session: Poster Display session 3
Resources:
Abstract
1922 - Expression of PD-L1 in plasma exosomes of NSCLC patients and its associations with PD-L1 expression of corresponding tumor tissues
Presenter: Shaorong Yu
Session: Poster Display session 3
Resources:
Abstract
5495 - Patient’s perspective on digital biomarkers in advanced urologic malignancies
Presenter: Severin Rodler
Session: Poster Display session 3
Resources:
Abstract
3166 - A comprehensive Pan-cancer study of FGFR Aberrations in Chinese cancer patients
Presenter: Yang Gao
Session: Poster Display session 3
Resources:
Abstract
3277 - A Systemic Inflammation Response Index (SIRI) correlates with survival and could be a Predictive Factor for mFOLFIRINOX in Metastatic Pancreatic Cancer (PC)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 3
Resources:
Abstract
2680 - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced Non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Presenter: Alberto Pavan
Session: Poster Display session 3
Resources:
Abstract
4066 - Breast cancer in young women of Kazakh population depending on germline mutations: results of next-generation sequencing
Presenter: Dilyara Kaidarova
Session: Poster Display session 3
Resources:
Abstract
5514 - Discovery of an ImmunoTranscriptomics signature in blood for early colorectal cancer detection
Presenter: Paolo Angelino
Session: Poster Display session 3
Resources:
Abstract
1595 - Serum Netrin-1 as a Biomarker for Colorectal Cancer Detection
Presenter: Jinzhou Zhu
Session: Poster Display session 3
Resources:
Abstract