Oncotarget: Analysis of primary tumors & paired brain metastases in lung cancer patients

Oncotarget published "Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study" which reported that Lung cancer brain metastases 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 and BMs. There is therefore a need for a better understanding of lung cancer BMs biology to improve treatment strategies for these patients.

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.

The Oncotarget authors provide some insights about the mechanisms leading to BMs and found recurrent mutations in BM samples in 13 genes.

The Oncotarget authors provide some insights about the mechanisms leading to BMs and 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 were described to be associated with the metastatic process.

Dr. Philippe Metellus from Marseille, France said, "Approximately 50% of brain metastases (BMs) are developed from lung cancers."

There is thus a need for a better biological understanding of lung cancer BMs to substantially improve treatment strategies in this field.

Recently, the identification of driver oncogenes and the development of targeted therapies have improved lung cancer patients' outcomes, especially for lung adenocarcinoma.

Figure 4: Lollipop plots for CRISP3, DRD5 and RUNX1T1 genes showing identified variants relative to a schematic representation of the gene. Colored boxes represent specific functional domains. Lollipop represents the variant identified; green lollipops stand for missense mutations and pink lollipops stand for silent mutations.

A pioneering study comparing genomic alterations in BMs and matched primary solid tumors; and showed that genomic alterations found in primary samples of solid tumors were not representative of BMs genomic characterization however, only few lung cancer samples were included.

Therefore, understanding lung cancer BMs biology is an actual need for better tailor treatment strategies in order to improve the outcome of patients with BMs from lung cancer.

The authors report a comprehensive analysis of genomic alterations in paired primary tumors and BMs in lung cancer patients and discuss their potential implications.

The Metellus Research Team concluded in their Oncotarget Research Output, "this work on BM from lung cancer is consistent with previous data comparing genomic profile of paired BM and primary samples of solid tumors. The results reported are of interest since new potential drivers involved in the BM process could be identified. Furthermore, this study offers new hypotheses and clues for further investigation of BMs biology in order to improve treatment strategies and outcomes of patients with BMs from lung cancers."

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DOI - https://doi.org/10.18632/oncotarget.27837

Full text - https://www.oncotarget.com/article/27837/text/

Correspondence to - Philippe Metellus - philippe.metellus@outlook.fr

Keywords - lung cancer, brain metastasis, whole exome sequencing, comparison, mutations

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