Transcriptome-Based Treatment for Melanoma With Brain Metastasis: A Case Report

TL;DR

This case report describes a personalized treatment approach for melanoma with brain metastasis using transcriptome analysis to identify gene markers and potential therapies.

Contribution

The study introduces a transcriptomics-based method to identify gene expression biomarkers and pathways for personalized treatment selection in melanoma with brain metastasis.

Findings

Transcriptome analysis identified 7 upregulated and 11 downregulated genes in blood, and 16 upregulated and 3 downregulated genes in tumor tissue.

CDK4 pathway overactivity was linked to potential inhibitors like ribociclib, abemaciclib, and palbociclib as putative treatments.

The approach showed 14% and 33% enrichment in blood and tissue, respectively, with 5 shared markers and 12 shared pathways.

Abstract

Malignant melanoma with brain metastasis has a high mortality rate. New approaches for diagnosis and treatment are urgently required to improve prognosis. Here we present a 60-year-old male with metastatic melanoma to the brain. Using a transcriptomics pipeline, we analyzed whole blood and resected tumor tissue, identifying enriched gene expression biomarkers and pathways - including seven upregulated ( BRAF, CDK4, EIF1AX, IK, NRAS, PIK3R2, and TP53) and 11 downregulated (CASP8, CDK10, CDKN2A, CTLA4, GNA11, HERC2, IRF4, MC1R, PLA2G6, RREB1, and TPCN2) genes in the blood (across 15 pathways), showing 14% enrichment, and 16 upregulated (CCND1, CDK4, CTLA4, EIF1AX, IK, IRF4, MITF, NRAS, PIK3CB, PIK3R2, PMEL, RREB1, SLC45A2, SOX10, TYR, and TYRP1) and three downregulated ( GNA11, KITLG, and PLA2G6) genes in tissue (across 17 pathways), showing 33% enrichment, with five shared markers and 12 shared pathways. The model connected CDK4 pathway overactivity observed in both samples to inhibitors like ribociclib, abemaciclib, and palbociclib as putative treatments. By enabling objective personalized therapy selection, this approach shows great promise for advancing patient outcomes.

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