Epco-01. the genomic landscape of brain metastasis

Abstract BACKGROUND The prognosis for patients with brain metastasis (BM) is devastating, while the underlying biology of BM development remains poorly understood. Identification of genomic biomarkers can offer promising opportunities for prediction of BM development and guidance in personalized treatment. In this study we evaluate the genomic alterations present in a large cohort of resected BM. METHODS Upon retrospective review, we identified 868 patients with diagnosis of solid primary cancers who had undergone a standard of care craniotomy at Memorial Sloan Kettering Cancer Center (MSKCC). BM samples were profiled by MSK-IMPACT, a next-generation sequencing (NGS) assay designed to detect a wide range of genetic alterations in 341-505 cancer genes. Genomic alterations were filtered for driver variants using OncoKB. Disease sites included cancers of head and neck, breast, lung, lower and upper gastrointestinal tract, kidney, ovary, uterus, prostate, skin, soft tissues, and others. RESULTS More than half (57%; 493/868) of patients were female and the median age was 63 (range 22-93). Foreseeably, the most common histology was non-small cell lung cancer (NSCLC; 38%), followed by invasive carcinoma of the breast and melanoma (16% and 13%, respectively). The most frequently encountered alterations were inTP53 (60%), CDKN2A (25%), TERT (23%), KRAS (18%), and PTEN (12%) across all BM samples. The median fraction of genome altered was 0.41 [range: 0-0.99] and the median tumor mutational burden was 6.6 muts/Mb [range: 0-395]. Additionally, TP53 was the most frequently altered gene after stratifying by primary histology in most cancer types, except for melanoma, renal, and thyroid, which were enriched for alterations in TERT, CDKN2A, and TERT, respectively. CONCLUSION The landscape of genomic alterations present in BM is distinct and varies by primary histologic diagnosis. Ongoing analyses of matched primary-BM pairs and clinicogenomic correlation will identify factors predisposing patients to BM development and progression.