Integrated Epigenetic and Transcriptomic Analysis Identifies Interleukin 17 DNA Methylation Signature of Malignant Peripheral Nerve Sheath Tumor Progression and Metastasis

Qierra R Brockman; Jeffrey D Rytlewski; Mohammed Milhem; Varun Monga; Rebecca D Dodd

doi:10.1200/PO.23.00325

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Integrated Epigenetic and Transcriptomic Analysis Identifies Interleukin 17 DNA Methylation Signature of Malignant Peripheral Nerve Sheath Tumor Progression and Metastasis

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Integrated Epigenetic and Transcriptomic Analysis Identifies Interleukin 17 DNA Methylation Signature of Malignant Peripheral Nerve Sheath Tumor Progression and Metastasis

Qierra R Brockman, Jeffrey D Rytlewski, Mohammed Milhem, Varun Monga and Rebecca D Dodd

JCO precision oncology, Vol.8, e2300325

05/2024

DOI: 10.1200/PO.23.00325

PMCID: PMC11552688

PMID: 38820476

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11552688/pdf/nihms-2024990.pdfView

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Abstract

Sarcomas are a complex group of highly aggressive and metastatic tumors with over 100 distinct subtypes. Because of their diversity and rarity, it is challenging to generate multisarcoma signatures that are predictive of patient outcomes. Here, we identify a DNA methylation signature for progression and metastasis of numerous sarcoma subtypes using multiple epigenetic and genomic patient data sets. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly metastatic sarcomas with frequent loss of the histone methyltransferase, PRC2. Loss of PRC2 is associated with MPNST metastasis and plays a critical noncanonical role in DNA methylation. We found that over 900 (CpGs) were hypermethylated in MPNSTs with PRC2 loss. Furthermore, we identified eight differentially methylated CpGs in the / family that correlate with the progression and metastasis of MPNSTs in two independent patient data sets. Similar trends were identified in other sarcoma subtypes, including osteosarcoma, rhabdomyosarcoma, and synovial sarcoma. Analysis of scRNAseq data sets determined that / expression occurs in both the tumor cells and the surrounding stromal populations. These results might have broad implications for the clinical management and surveillance of sarcoma.

Disease Progression

DNA Methylation

Epigenesis, Genetic

Gene Expression Profiling

Humans

Interleukin-17 - genetics

Neoplasm Metastasis - genetics

Nerve Sheath Neoplasms - genetics

Nerve Sheath Neoplasms - pathology

Neurofibrosarcoma - genetics

Neurofibrosarcoma - pathology

Transcriptome

Details

Title: Subtitle: Integrated Epigenetic and Transcriptomic Analysis Identifies Interleukin 17 DNA Methylation Signature of Malignant Peripheral Nerve Sheath Tumor Progression and Metastasis
Creators: Qierra R Brockman - University of Iowa
Jeffrey D Rytlewski - University of Iowa
Mohammed Milhem - University of Iowa
Varun Monga - University of California, San Francisco
Rebecca D Dodd - University of Iowa
Resource Type: Journal article
Publication Details: JCO precision oncology, Vol.8, e2300325
DOI: 10.1200/PO.23.00325
PMID: 38820476
PMCID: PMC11552688
NLM abbreviation: JCO Precis Oncol
eISSN: 2473-4284
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Grant note: DAS:No data sets were generated during the current study. The data sets analyzed during the current study are available in the GEO, dbGaP repository, or EGA archive: GSE140686 (DNA methylation data; Data Supplement, Table S1), phs000792.v1.p1 (MPNST RNAseq; Data Supplement, Table S2), GSE183308 (MPNST scRNAseq data; Data Supplement, Table S3), and EGAD00001008608 (MPNST DNA methylation w/NF1-status).
Language: English
Date published: 05/2024
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984634159002771

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