Mutational landscape and evolutionary pattern of liver and brain metastasis in lung adenocarcinoma
Menée à partir du séquençage de l'ensemble de l'exome de tissus tumoraux et d'échantillons sanguins prélevés sur 26 patients atteints d'un adénocarcinome pulmonaire, cette étude compare les caractéristiques mutationnelles des lésions primitives avec celles des métastases hépatiques et des métastases cérébrales, puis compare l'évolution génétique de ces deux types de métastases
Introduction : Comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships among diverse metastatic lesions from one cancer remains limited. Methods : Here, we performed whole-exome sequencing in 84 tissue and blood samples from 26 lung adenocarcinoma patients with liver or brain metastases (LiM or BrM) before any systemic therapy, with the goal to molecularly characterize the metastatic process. Mutational landscape and evolutionary patterns were compared between paired primary lesions (LiM-P or BrM-P) and metastases (LiM-M or BrM-M). Results : We found that common driver mutations including TP53 and EGFR were highly consistent between paired primary and metastatic tumors. Although tumor mutational burden was comparable among groups, LiM group had significantly higher mutational and copy number variational similarity than BrM group between paired primary lesions and metastases ( P = 0.019, P = 0.035; respectively). Phylogenetic analysis further revealed that LiM-competent disseminations had higher level of genetic similarity to their paired primary lesions and genetically diverged from their primary tumors at relatively later stage than those of BrM, suggesting that LiM favorably followed the linear progression model whereas BrM was more consistent with the parallel progression model. Conclusions : The current study suggested that the mutational landscape and evolutionary pattern was distinctly different between the LiM and BrM of lung adenocarcinoma.