Your browser doesn't support javascript.
loading
DNA Methylation Signatures Correlate with Response to Immune Checkpoint Inhibitors in Metastatic Melanoma.
Ressler, Julia Maria; Tomasich, Erwin; Hatziioannou, Teresa; Ringl, Helmut; Heller, Gerwin; Silmbrod, Rita; Gottmann, Lynn; Starzer, Angelika Martina; Zila, Nina; Tschandl, Philipp; Hoeller, Christoph; Preusser, Matthias; Berghoff, Anna Sophie.
Affiliation
  • Ressler JM; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Tomasich E; Department of Medicine I, Division of Oncology, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Hatziioannou T; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
  • Ringl H; Department of Medicine I, Division of Oncology, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Heller G; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
  • Silmbrod R; Wiener Gesundheitsverbund, Klinik Donaustadt, Vienna, Austria.
  • Gottmann L; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
  • Starzer AM; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Zila N; Department of Medicine I, Division of Oncology, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Tschandl P; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
  • Hoeller C; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
  • Preusser M; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Berghoff AS; Division of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna, Austria.
Target Oncol ; 19(2): 263-275, 2024 Mar.
Article in En | MEDLINE | ID: mdl-38401029
ABSTRACT

BACKGROUND:

DNA methylation profiles have emerged as potential predictors of therapeutic response in various solid tumors.

OBJECTIVE:

This study aimed to analyze the DNA methylation profiles of patients with stage IV metastatic melanoma undergoing first-line immune checkpoint inhibitor treatment and evaluate their correlation with a radiological response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).

METHODS:

A total of 81 tissue samples from 71 patients with metastatic melanoma (27 female, 44 male) were included in this study. We utilized Illumina Methylation EPIC Beadchips to retrieve their genome-wide methylation profile by interrogating >850,000 CpG sites. Clustering based on the 500 most differentially methylated genes was conducted to identify distinct methylation patterns associated with immune checkpoint inhibitor response. Results were further aligned with an independent, previously published data set.

RESULTS:

The median progression-free survival was 8.5 months (range 0-104.1 months), and the median overall survival was 30.6 months (range 0-104.1 months). Objective responses were observed in 29 patients (40.8%). DNA methylation profiling revealed specific signatures that correlated with radiological response to immune checkpoint inhibitors. Three distinct clusters were identified based on the methylation patterns of the 500 most differentially methylated genes. Cluster 1 (12/12) and cluster 2 (12/24) exhibited a higher proportion of responders, while cluster 3 (39/45) predominantly consisted of non-responders. In the validation data set, responders also showed more frequent hypomethylation although differences in the data sets limit the interpretation.

CONCLUSIONS:

These findings suggest that DNA methylation profiling of tumor tissues might serve as a predictive biomarker for immune checkpoint inhibitor response in patients with metastatic melanoma. Further validation studies are warranted to confirm the efficiency of DNA methylation profiling as a predictive tool in the context of immunotherapy for metastatic melanoma.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Melanoma Limits: Female / Humans / Male Language: En Journal: Target Oncol Journal subject: NEOPLASIAS Year: 2024 Document type: Article Affiliation country: Austria Country of publication: France

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Melanoma Limits: Female / Humans / Male Language: En Journal: Target Oncol Journal subject: NEOPLASIAS Year: 2024 Document type: Article Affiliation country: Austria Country of publication: France