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Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma

Vízkeleti, Laura ; Papp, Orsolya ; Doma, Viktória ; Gil, Jeovanis LU orcid ; Markó-Varga, György LU ; Kovács, Szonja A. ; Győrffy, Balázs ; Kárpáti, Sarolta and Tímár, József (2024) In Scientific Reports 14(1).
Abstract

Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic progression. We run genome-wide copy number variation (CNV) analysis on previously type-I IFN-treated (n = 17) and control (n = 11) visceral metastases of melanoma patients. Results were completed with data from the TCGA and MM500 databases. We identified metastasis- and brain metastasis-specific gene signatures mostly affected by CN gains. Some cases were genetically resistant to IFN showing characteristic gene alterations (e.g. ABCA4 or ZEB2 gain and... (More)

Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic progression. We run genome-wide copy number variation (CNV) analysis on previously type-I IFN-treated (n = 17) and control (n = 11) visceral metastases of melanoma patients. Results were completed with data from the TCGA and MM500 databases. We identified metastasis- and brain metastasis-specific gene signatures mostly affected by CN gains. Some cases were genetically resistant to IFN showing characteristic gene alterations (e.g. ABCA4 or ZEB2 gain and alterations of DNA repair genes). Analysis of a previously identified type-I IFN resistance gene set indicates that only a proportion of these genes was exclusive for the IFN-treated metastases reflecting a possible selective genomic pressure of endogenous IFNs during progression. Our data suggest that previous type-I IFN treatment and/or endogenous IFN production by immune response affect genomic progression of melanoma which may have clinical relevance, potentially influence immune checkpoint regulation in the tumor microenvironment.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CNV, Malignant melanoma, Type-I interferon, Visceral metastases
in
Scientific Reports
volume
14
issue
1
article number
26540
publisher
Nature Publishing Group
external identifiers
  • pmid:39489756
  • scopus:85208470617
ISSN
2045-2322
DOI
10.1038/s41598-024-77285-x
language
English
LU publication?
yes
id
2bfdc49c-5f1e-45a3-8765-1f76929915df
date added to LUP
2025-01-09 15:28:27
date last changed
2025-07-11 20:08:34
@article{2bfdc49c-5f1e-45a3-8765-1f76929915df,
  abstract     = {{<p>Malignant melanoma is a difficult-to-treat skin cancer with increasing incidence worldwide. Although type-I interferon (IFN) is no longer part of guidelines, several melanoma patients are treated with type-I interferon (IFN) at some point of the disease, potentially affecting its genetic progression. We run genome-wide copy number variation (CNV) analysis on previously type-I IFN-treated (n = 17) and control (n = 11) visceral metastases of melanoma patients. Results were completed with data from the TCGA and MM500 databases. We identified metastasis- and brain metastasis-specific gene signatures mostly affected by CN gains. Some cases were genetically resistant to IFN showing characteristic gene alterations (e.g. ABCA4 or ZEB2 gain and alterations of DNA repair genes). Analysis of a previously identified type-I IFN resistance gene set indicates that only a proportion of these genes was exclusive for the IFN-treated metastases reflecting a possible selective genomic pressure of endogenous IFNs during progression. Our data suggest that previous type-I IFN treatment and/or endogenous IFN production by immune response affect genomic progression of melanoma which may have clinical relevance, potentially influence immune checkpoint regulation in the tumor microenvironment.</p>}},
  author       = {{Vízkeleti, Laura and Papp, Orsolya and Doma, Viktória and Gil, Jeovanis and Markó-Varga, György and Kovács, Szonja A. and Győrffy, Balázs and Kárpáti, Sarolta and Tímár, József}},
  issn         = {{2045-2322}},
  keywords     = {{CNV; Malignant melanoma; Type-I interferon; Visceral metastases}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Identification of genetic fingerprint of type I interferon therapy in visceral metastases of melanoma}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-77285-x}},
  doi          = {{10.1038/s41598-024-77285-x}},
  volume       = {{14}},
  year         = {{2024}},
}