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
5056 - Phase 2 study of 2 dosing regimens of cemiplimab, a human monoclonal anti–PD-1, in metastatic cutaneous squamous cell carcinoma (mCSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
5710 - Avelumab for advanced Merkel cell carcinoma in the Netherlands; a nationwide survey
Presenter: Sonja Levy
Session: Poster Display session 3
Resources:
Abstract
3152 - Health-related quality of life in patients with metastatic Merkel cell carcinoma receiving second-line or later avelumab treatment: 36-month follow-up data
Presenter: Sandra D'Angelo
Session: Poster Display session 3
Resources:
Abstract
5715 - A Phase 2, Randomized Study of Nivolumab (NIVO) and Ipilimumab (IPI) versus NIVO, IPI and Stereotactic Body Radiation Therapy (SBRT) for Metastatic Merkel Cell Carcinoma (MCC, NCT03071406) – a preliminary report.
Presenter: Sungjune Kim
Session: Poster Display session 3
Resources:
Abstract
2854 - Real-world impact of immune checkpoint inhibitors in metastatic uveal melanoma
Presenter: Kalijn Bol
Session: Poster Display session 3
Resources:
Abstract
2928 - Immune checkpoint inhibitors in a cohort of 206 metastatic uveal melanomas patients
Presenter: Mathilde Saint-Ghislain
Session: Poster Display session 3
Resources:
Abstract
1235 - Incidence and survival of Uveal Melanoma occurring as single cancer versus its occurrence as a first or second primary neoplasm
Presenter: Ahmad Alfaar
Session: Poster Display session 3
Resources:
Abstract
3615 - Validation of a Clinicopathological and Gene Expression Profile (CP-GEP) Model for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
Presenter: Evalyn Mulder
Session: Poster Display session 3
Resources:
Abstract
1793 - External validation of the 8th Edition Melanoma Staging System of the American Joint Committee on Cancer (AJCC) using the Surveillance, Epidemiology and End Results (SEER) Program
Presenter: Angelina Tjokrowidjaja
Session: Poster Display session 3
Resources:
Abstract
4278 - Clinical factors and overall survival (OS) associated with patterns of metastases (mets) in melanoma patients (pts).
Presenter: Ines Pires da Silva
Session: Poster Display session 3
Resources:
Abstract