Abstract 4111
Background
Molecular heterogeneity drives tumour evolution and resistance to therapies. Because of biopsy challenges in non-small cell lung cancer (NSCLC), few studies compared the molecular profile between primary tumour (PT) and metastasis (Met). Here, we compare somatic single-nucleotide variants (SNVs), tumour mutational burden (TMB) and expression profiles between PT and matched metachronous Met in NSCLC patients (pts).
Methods
DNA and RNA were extracted from 14 matched fresh-frozen samples and PBMCs from 7 pts treated at the Institut d’Oncologie Thoracique (Gustave Roussy, GR) between 2011 and 2015. GATK4 Mutect2 were used for SNV calling and TMB on whole exome sequencing. Salmon was used for expression counts from RNAseq; Z-scores were computed by comparing data to 158 other NSCLC RNAseq from GR molecular profiling trials; GSVA R package was use to assess single sample gene set enrichment score (ssGSEA).
Results
Median age was 67 yo (62-78); 4/7 metastases were biopsied after chemotherapy; histology was adenocarcinoma (6) or large cell carcinoma (1). The median number of SNVs unique to PT or Met was 50 (10-143) or 79 (36-324), respectively; it was 65 (0-110) for shared SNVs; 6/7 pts had known driver alterations (TP53, KRAS, PIK3CA) in both lesions; one Met acquired a pathogenic KRAS G35C mutation. Median TMB was 3.9 (0.3-4.3) in PT and 4.1 (2.2-8.4) in Met. Genes with top negative Z-scores (MRFAP1, EP400, RIOX1, DDX27) were shared between PT and Met in 6/7 pts; genes with top positive Z-score were unique. ssGSEA-enriched genesets were shared between PT and Met; top enriched hallmarks included Myc targets, Mitotic Spindle, DNA repair, oxidative phosphorylation and TGFb signaling.
Conclusions
Matched comparison of molecular profiles between PT and Met evidence shared and unique alterations; this informs on tumor evolution and may help guiding treatment choice.
Clinical trial identification
Editorial acknowledgement
AK: AK was funded by the DUERTECC Gustave Roussy program
LCD: LCD was funded by the INSERM ATIP-Avenir grant from SPV
Legal entity responsible for the study
Sophie Postel-Vinay.
Funding
Cancéropole d’Ile de France.
Disclosure
A Kawachi: Funded by the DUERTECC Gustave Roussy program. L. Colmet-Daage: Funded by the INSERM ATIP-Avenir grant from SPV. L. Verlingue: Honoraria (self): Adaptherapy; Research grant / Funding (self): Bristol-Myers Squibb. D. Planchard: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): prIME Oncology; Honoraria (self): Peer CME; Honoraria (self): Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Boehringer Ingelheim ; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: prIME Oncology; Travel / Accommodation / Expenses: Pfizer. A. Hollebecque: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi. C. Massard: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Janssen Cilag; Research grant / Funding (self): Merck, Novartis; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Lilly. B. Besse: Research grant / Funding (self): Abbvie; Research grant / Funding (self): Amgen; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Biogen; Research grant / Funding (self): Blueprint Medicines; Research grant / Funding (self): BMS; Research grant / Funding (self): Celgene; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): GSK; Research grant / Funding (self): Ignyta; Research grant / Funding (self): IPSEN; Research grant / Funding (self): Merck KGaA; Research grant / Funding (self): MSD; Research grant / Funding (self): Nektar; Research grant / Funding (self): Onxeo; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Pharma Mar; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Spectrum Pharmaceuticals; Research grant / Funding (self): Takeda. J. Soria: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Astex; Advisory / Consultancy: Clovis; Advisory / Consultancy: GSK; Advisory / Consultancy: GamaMabs; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Mission Therapeutics; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Takeda; Full / Part-time employment: AstraZeneca. S. Postel Vinay: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Janssen Cilag; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi. All other authors have declared no conflicts of interest.
Resources from the same session
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract