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In GK , Poorman K , Saul M , O'Day S , Farma JM , Olszanski AJ , Gordon MS , Thomas JS , Eisenberg B , Flaherty L , Weise A , Daveluy S , Gibney G , Atkins MB , Vanderwalde A
Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases
Oncotarget. 2020 Aug 18;11(33) :3118-3128
PMID: 32913556    PMCID: PMC7443369   
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BACKGROUND: Brain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases. MATERIALS AND METHODS: We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM. RESULTS: The most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency among MBM compared to PCM or ECM: BRAF (52.4% v 40.4% v 40.9%), SETD2 (11.9% v 1.9% v 3.9%), PBRM1 (7.5% v 1.6% v 2.6%), and DICER1 (4.4% v 0.6% v 0.4%). MBM showed higher TMB (p = .04) and higher PD-L1 expression (p = .002), compared to PCM. PD-L1 expression was slightly higher among MBM compared to ECM (p = .042), but there was no difference between TMB (p = .21). CONCLUSIONS: Our findings suggest a unique molecular profile for MBM, including higher rates of BRAF mutations, higher TMB and higher PD-L1 expression, and also implicate chromatin remodeling in the pathogenesis of MBM.
1949-2553 In, Gino K Poorman, Kelsey Saul, Michelle O'Day, Steven Farma, Jeffrey M Olszanski, Anthony J Gordon, Michael S Thomas, Jacob S Eisenberg, Burton Flaherty, Lawrence Weise, Amy Daveluy, Steven Gibney, Geoffrey Atkins, Michael B Vanderwalde, Ari Journal Article Oncotarget. 2020 Aug 18;11(33):3118-3128. doi: 10.18632/oncotarget.27686. eCollection 2020 Aug 18.