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

Pascale Tomasini (1, 2) , Fabrice Barlesi (1, 2) , Sophie Gilles (3) , Isabelle Nanni-Metellus (3) , Riccardo Soffietti (4) , Emilie Denicolai (5) , Eric Pellegrino (3) , Emilie Bialecki (6) , L'Houcine Ouafik (7, 3) , Philippe Metellus (6, 7)

1 Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
2 AMU - Aix Marseille Université
3 Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM]
4 City of Health and Science University Hospital [Turin, Italy]
5 CRCM - Centre de Recherche en Cancérologie de Marseille
6 Hôpital Privé Clairval [Marseille]
7 INP - Institut de neurophysiopathologie

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.

Mots clés: lung cancer; brain metastasis; whole exome sequencing; comparison; mutations

Domaines: Cancer

Pascale Tomasini, Fabrice Barlesi, Sophie Gilles, Isabelle Nanni-Metellus, Riccardo Soffietti, et al.. Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study. Oncotarget, 2020, 11 (50), pp.4648-4654. ⟨10.18632/oncotarget.27837⟩. ⟨hal-03105754⟩