Mutational signatures of synchronous and metachronous brain metastases from lung adenocarcinoma

Brain metastasis (BM) is an important cause of mortality for cancer patients. Many patients were diagnosed with brain metastases at their first visit who have not received any treatment while a subset of patients did not have distant metastases at the first visit and brain metastases were detected during the course of systemic therapies. The difference in their genomic characterization is unclear. 96 lung adenocarcinoma patients were enrolled in our study. 53 patients (55%) had synchronous metastatic brain tumors. 43 (45%) patients had metachronous brain metastases. We performed 168 panel-targeted gene sequencing cerebrospinal fluid (CSF) and plasma samples from patients to identify genomic features of synchronous brain metastases (SBM) and metachronous brain metastases (MBM). In conclusion, CSF liquid biopsies have a priority in detecting gene alteration. A comprehensive comparison of molecular profiling between SBM and MBM revealed the most frequently altered genes in both groups were EGFR and TP53, but with different exon point mutations. RTK-RAS and TP53 pathways were the most affected pathways.

Automated summary

Brain metastasis is a major cause of cancer-related death. Some patients are diagnosed with brain metastases at their first visit without prior treatment, while others develop brain metastases during systemic therapies. The genomic differences between these two groups are unclear. In this study, we analyzed the genomic features of synchronous and metachronous brain metastases in lung adenocarcinoma patients using panel-targeted gene sequencing of cerebrospinal fluid and plasma samples. CSF liquid biopsies were found to be superior in detecting gene alterations. EGFR and TP53 were the most frequently altered genes in both groups, but with different exon point mutations. The RTK-RAS and TP53 pathways were identified as the most affected pathways.