Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study
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Pascale Tomasini1,2, Fabrice Barlesi1,2, Sophie Gilles3, Isabelle Nanni-Metellus3, Riccardo Soffietti4, Emilie Denicolai2, Eric Pellegrino3, Emilie Bialecki5, L’Houcine Ouafik3,6 and Philippe Metellus5,6
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
Keywords: lung cancer; brain metastasis; whole exome sequencing; comparison; mutations
Received: August 07, 2020 Accepted: November 19, 2020 Published: December 15, 2020
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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