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.
Highlights
50% of brain metastases (BMs) are developed from lung cancers [1]
A majority of putatively somatic variants found in primary tumors were found in BM samples as 19 mutations only were found to be specific of primary tumors (Figure 1B)
This is especially true for lung cancer since it is the leading cause of BMs, with frequent discrepancies observed between systemic response and intracranial response to treatments
Summary
50% of brain metastases (BMs) are developed from lung cancers [1]. In autopsy series, up to 50% lung cancer patients were found with BMs [2]. The median overall survival (OS) of patients with BMs from adenocarcinoma of the lung is short (4 to 11 weeks) [2, 3]. With treatments such as neurosurgery, stereotactic radiosurgery and whole brain radiation therapy or systemic treatments OS has improved but remains limited (6.9–13.7 months) [4]. There is a need for a better biological understanding of lung cancer BMs to substantially improve treatment strategies in this field
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call