1479OIntegrated genomic and DNA methylation analyses of non-small cell lung cancer patients with brain metastases

Abstract Background Brain metastases (BM), with a dismal prognosis, are a common and lethal complication of non-small cell lung cancer. Recognition of its genomic and epigenomic landscape is very necessary. Methods Capture-based targeted sequencing for somatic mutation profiling was performed on 27 treatment-naive advanced NSCLC patients with paired lung primary and BM lesions using a pane consisting of 520 cancer related genes. DNA methylation analyses was performed on same samples using a DNA methylation panel consisting of 100,000 CpG sites. Results Collectively, we identified 370 (291 SNVs+Indels, 78 CNVs and 1 rearrangement) and 574 (245 SNVs+Indels, 327 CNVs and 2 rearrangements) mutations from lung primary lesions and BM, respectively. Among them, 242 mutations were shared; 128 were lung primary-specific and 332 were BM-specific. Among the BM specific mutations, a majority of them (82%, 272/332) were copy number variations (CNVs). Only 16% of CNVs were shared by lung lesions and BM. The concordance for SNVs and indels were much higher-54% between the two sources of tissues. Furthermore, we observed a much higher concordance rate (79%) in TP53 and classic lung cancer driver genes than other genes (p  Conclusions We revealed diverse somatic mutation and DNA methylation profiles between lung primary lesions and BM. BM had significantly more unique CNVs. A great concordance was observed for classic lung cancer driver genes and TP53. Our study provided a comprehensive view of genomic and DNA methylation profiling for lung primary lesions and BM, paving the avenue for the development of targeted therapies for treating BM. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.