OTHR-06. ANALYSIS OF GENOMIC ALTERATIONS IN 154 BRAIN METASTASES

Abstract Brain Metastases (BM) are associated with poor prognosis. Understanding the genomic alterations (GA) that drive tumor metastasis to the brain will increase our ability to identify patients at risk for BM, and provide better opportunities to implement targeted therapies. We performed a retrospective review of genomic alterations in 154 patients with BM from various primary sites (80 Lung, 22 Breast, 16 Melanoma, 5 Kidney, 4 Colorectal, 4 Prostate, and 23 carcinomas from unknown primary (UP). All cases were analyzed by a next generation sequencing assay the detects mutations in the coding region of 327 genes and rearrangements involving 37 genes. The most commonly mutated genes were; TP53, CDKN2A/B, KRAS, MYC, RB1, NF1, PIKC3A, STK11, and PTEN. A comparison of GA in our BM cases with unmatched primary tumors from COSMIC revealed differences in the frequency of mutated genes: TP53 (Lung 85% vs 38%, Breast 63.6% vs 26.0%) CDKN2A/B (Lung 33.7% vs 7%, Melanoma 56.2% vs 18%, Kidney 40% vs 2%, UC 34.7% vs 9%), ERBB2 (Breast 36.3% vs 4%), MYC (Breast 36.36% vs 0.3%), TERT (Melanoma 62.5% vs 25%, Kidney 40% vs 2%), APC (Colon 100% vs 48%), KRAS (Colon 100% vs 31%), PTEN (Prostate 50% vs 7%), TSC1 (Kidney 40% vs 2%), STK11 (UC 26.0% vs 6%). Our results demonstrate a higher frequency of TP53 mutations (p=0.001) in metastatic lung cancer, and a higher frequency of MYC amplification (p=0.01) in metastatic breast cancer, when compared to primary tumors. The present study demonstrates significant differences in the frequency of mutations between primary tumors and BM. Such differences may play an important role in the pathogenesis of BM and may allow for targeted strategies utilizing existing therapies.