Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study

Abstract

// Pascale Tomasini 1 , 2 , Fabrice Barlesi 1 , 2 , Sophie Gilles 3 , Isabelle Nanni-Metellus 3 , Riccardo Soffietti 4 , Emilie Denicolai 2 , Eric Pellegrino 3 , Emilie Bialecki 5 , L’Houcine Ouafik 3 , 6 and Philippe Metellus 5 , 6 1 Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations Department, Marseille, France 2 Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR7258, Aix-Marseille Université UM105, Marseille, France 3 Aix Marseille University, Assistance Publique Hôpitaux de Marseille, CHU Nord, Service de Transfert d’Oncologie Biologique, Marseille, France 4 Department of Neuro Oncology, University and City of Health and Science Hospital, Turin, Italy 5 Ramsay Santé, Hôpital Privé Clairval, Département de Neurochirurgie, Marseille, France 6 Aix-Marseille University, CNRS UMR 7051, Institut de Neurophysiopathologie, Marseille, France Correspondence to: Philippe Metellus, email: [email protected] Keywords: lung cancer; brain metastasis; whole exome sequencing; comparison; mutations Received: August 07, 2020     Accepted: November 19, 2020     Published: December 15, 2020 Copyright: © 2020 Tomasini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Lung cancer brain metastases (BMs) are frequent and associated with poor prognosis despite a better knowledge of lung cancer biology and the development of targeted therapies. The inconstant intracranial response to systemic treatments is partially due to tumor heterogeneity between the primary lung tumor (PLT) and BMs. There is therefore a need for a better understanding of lung cancer BMs biology to improve treatment strategies for these patients. We conducted a study of whole exome sequencing of paired BM and PLT samples. The number of somatic variants and chromosomal alterations was higher in BM samples. We identified recurrent mutations in BMs not found in PLT. Phylogenic trees and lollipop plots were designed to describe their functional impact. Among the 13 genes mutated in ≥ 1 BM, 7 were previously described to be associated with invasion process, including 3 with recurrent mutations in functional domains which may be future targets for therapy. We provide with some insights about the mechanisms leading to BMs. We found recurrent mutations in BM samples in 13 genes. Among these genes, 7 were previously described to be associated with cancer and 3 of them ( CCDC178 , RUNX1T1 , MUC2 ) were described to be associated with the metastatic process.

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