In addition to putative pathogenic alterations in NSCLC-BM that could be targeted by existing drugs, our study also revealed a substantial enrichment of SCNAs and mutations in genes encoding for histone methyltransferases (KMT2A, KMT2C, KMT2D, SETD2, SETD1B), histone acetyltransferases (EP300, KAT6B), chromatin remodeling factors (PBMR1), and 3D genome shapers (CTCF, STAG1/2) in NSCLC-BM compared with primary NSCLC tumors. Here, SET is linked to non-small cell lung carcinoma.