ArticleCancer genomics & proteomics
Characterization of the Neoantigen Profile in a Tumor Mutation Burden-high Melanoma Patient With Multiple Metastases.
Article in Cancer genomics & proteomics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- mRNA-based melanoma vaccines targeting gp100 and TRP2 macromolecules.Discover oncology · 2026Review
- Molecular Dynamics Simulation Analysis of JAK1 Initial Activation: Phosphorylation-Induced Conformational Dynamics and Domain Interactions.Life (Basel, Switzerland) · 2025Article
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Authors and funding
15 authors.
Funding
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Abstract
BACKGROUND/
aimRecently, neoantigen (NA) profiling has been intensively performed for the development of novel immunotherapy. We previously reported a melanoma case with a high tumor mutation burden that achieved complete remission after anti-programmed death-1 therapy. We herein revisited the same case, characterized the NA profiles of other metastatic lesions using MATERIALS AND
methodsNA candidates obtained from whole-exome sequencing were applied to the HLA-binding prediction algorithm, NetMHCpan4.1. HLA-A*2402-restricted sequence candidates with a strong binding capacity (<50 nM) and elution affinity (<1%) were selected and evaluated for synthetic peptide candidates. The immunological status in metastatic sites was characterized using gene expression profiling, immunohistochemistry, and a TCR repertoire analysis.
resultsThe genomic analysis revealed that all metastatic sites, such as costal, intra-muscular, and brain lesions, had >1,500 SNVs, and 12 driver mutations were common to all sites. New driver mutations were identified in intra-muscular (KMT2C: p.P3292S) and brain (JAK1: p.S404P) metastases and a functional analysis of these mutations revealed that JAK1 mutation exhibited a promoting effect on invasion activity. CTL assays using synthetic NA peptides identified more NA epitopes in brain metastasis.
conclusionThese results might suggest that the heterogeneity of driver gene mutations is unremarkable, while immunological response is variable in metastatic sites. As a result, the genomic and immunological investigation has provided a very valuable and informative suggestion regarding better cancer therapy decisions.
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