Unravelling genomic differences in cerebrospinal fluid: patients with lung cancer with combined brain parenchymal and meningeal metastasis versus exclusive meningeal metastasis.

OBJECTIVE: This study aimed to compare and analyse the genomic features in cerebrospinal fluid (CSF) between patients with both brain parenchymal metastasis (BM) and meningeal metastasis (MM) of lung cancer and patients with MM only. METHODS: 34 patients with lung adenocarcinoma were included in this study, including 18 patients in the BM&MM group, 12 in the MM group and 4 in the BM group. The genomic characteristics were compared by circulating tumour DNA (ctDNA) detection in CSF and plasma samples. RESULTS: The positive rate of ctDNA detection in the CSF was significantly higher than that in plasma, and the variation detected in the CSF was more abundant, especially epidermal growth factor receptor (EGFR) mutation (p < 0.05). The consistency detected between the CSF and plasma was poor. There was no significant difference in the tumour mutation burden between the BM&MM and MM groups, and no significant differential mutations were found by mutation mapping and pathway enrichment analysis (p > 0.05). In the BM&MM group, there was a significant co-mutation relationship between RB1 and ERBB4, MTOR and ATM, MLH3 and CTNNB1 and TP53 and EGFR; in the MM group, there was a strong co-exclusion of EGFR and KRAS mutations. Chromosomal copy number variation analysis showed significant amplification in the MM group at the p15.33 bands on chromosome 5 and the 7p11.2 bands on chromosome 7. In the comparative analysis of tumour markers and CSF biochemical parameters between the two groups, no significant differences were found. CONCLUSION: This study revealed significant differences in CSF genomic characteristics between patients with simultaneous BM and MM of lung cancer and patients with MM only. These differences provide potential biomarkers for the precise treatment of patients with brain metastases and help to distinguish patients with lung cancer brain metastases with different metastatic patterns.