Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases.
BRAF
PD-L1
TMB
brain metastases
melanoma
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
18 Aug 2020
18 Aug 2020
Historique:
received:
25
03
2020
accepted:
07
07
2020
entrez:
11
9
2020
pubmed:
12
9
2020
medline:
12
9
2020
Statut:
epublish
Résumé
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. We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM. 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 ( 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.
Sections du résumé
BACKGROUND
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
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
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 (
CONCLUSIONS
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.
Identifiants
pubmed: 32913556
doi: 10.18632/oncotarget.27686
pii: 27686
pmc: PMC7443369
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3118-3128Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST GKI: Advisory boards/Consulting: Sanofi, BMS, Novartis. Speaker: Merck. Clinical Trials: Genentech, Idera. KP, MS: Employed by Caris Life Sciences. SOD: Advisory boards/Consulting: Agenus, Biothera, BMS, Biontech, Exicure, Immunsys, Merck. Speaker: BMS. JMF: Advisory boards/Consulting: Novartis, Delcath. GG: Advisory boards/Consulting: Novartis, BMS, Regeneron. Clinical trials: Exelixis. Trial steering committee (non-compensated) Genentech. MBA: Advisory board/Consulting: BMS, Merck, Novartis, Arrowhead, Pfizer, Galactone, Werewolf, Fathom, Pneuma, Leads, Pyxis Oncology, PACT, Genentech, Exelixis, Eisai, Aveo, Array, ImmunoCore, Boehringer-Ingelheim, Iovance, Newlink, Surface, Cota. Clinical Trials: Merck, Pfizer, BMS, X4P, Genentech, Aveo. Research support: BMS, Merck, Pfizer. Stock options: Werewolf, Pyxis Oncology. AVW: Consulting/Advisory boards: AstraZeneca, BMS, Caris Life Sciences, ConcertoHealthAI. Research support: Amgen, Caris Life Sciences. All other authors: none.
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