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Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases
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 meta...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443369/ https://www.ncbi.nlm.nih.gov/pubmed/32913556 http://dx.doi.org/10.18632/oncotarget.27686 |
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author | 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 |
author_facet | 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 |
author_sort | In, Gino K. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7443369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-74433692020-09-09 Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases 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 Oncotarget Research Paper 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. Impact Journals LLC 2020-08-18 /pmc/articles/PMC7443369/ /pubmed/32913556 http://dx.doi.org/10.18632/oncotarget.27686 Text en http://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Paper 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 Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
title | Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
title_full | Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
title_fullStr | Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
title_full_unstemmed | Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
title_short | Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
title_sort | molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443369/ https://www.ncbi.nlm.nih.gov/pubmed/32913556 http://dx.doi.org/10.18632/oncotarget.27686 |
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