TY - JOUR
T1 - Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases
AU - In, Gino K.
AU - Poorman, Kelsey
AU - Saul, Michelle
AU - O'Day, Steven
AU - Farma, Jeffrey M.
AU - Olszanski, Anthony J.
AU - Gordon, Michael S.
AU - Thomas, Jacob S.
AU - Eisenberg, Burton
AU - Flaherty, Lawrence
AU - Weise, Amy
AU - Daveluy, Steven
AU - Gibney, Geoffrey
AU - Atkins, Michael B.
AU - Vanderwalde, Ari
N1 - Publisher Copyright:
Copyright: © In et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/8/18
Y1 - 2020/8/18
N2 - 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.
AB - 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.
KW - BRAF
KW - Brain metastases
KW - Melanoma
KW - PD-L1
KW - TMB
UR - http://www.scopus.com/inward/record.url?scp=85091120934&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.27686
DO - 10.18632/oncotarget.27686
M3 - Article
C2 - 32913556
AN - SCOPUS:85091120934
SN - 1949-2553
VL - 11
SP - 3118
EP - 3128
JO - Oncotarget
JF - Oncotarget
IS - 33
ER -