DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness

  1. Arnaud Carrier
  2. Cécile Desjobert
  3. Loic Ponger
  4. Laurence Lamant
  5. Matias Bustos
  6. Jorge Torres-Ferreira
  7. Rui Henrique
  8. Carmen Jeronimo
  9. Luisa Lanfrancone
  10. Audrey Delmas
  11. Gilles Favre
  12. Antoine Delaunay
  13. Florence Busato
  14. Dave SB Hoon
  15. Jorg Tost
  16. Chantal Etievant
  17. Joëlle Riond
  18. Paola B Arimondo  Is a corresponding author
  1. CNRS-Pierre Fabre, France
  2. CNRS UMR 7196, INSERM U1154, France
  3. UMR 1037, INSERM, Université Toulouse III Paul Sabatier, France
  4. Providence Saint John's Health Center, United States
  5. Portuguese Oncology Institute, Portugal
  6. Instituto Europeo di Oncologia, Italy
  7. Fondation Jean Dausset-CEPH, France
  8. CNRS, CEA-Institut de Biologie François Jacob, France
  9. Institut Pasteur, CNRS UMR 3523, France

Abstract

Aberrant DNA methylation is a well‑known feature of tumours and has been associated with metastatic melanoma. However, since melanoma cells are highly heterogeneous, it has been challenging to use affected genes to predict tumour aggressiveness, metastatic evolution, and patients' outcomes. We hypothesized that common aggressive hypermethylation signatures should emerge early in tumorigenesis and should be shared in aggressive cells, independent of the physiological context under which this trait arises. We compared paired melanoma cell lines with the following properties: (i) each pair comprises one aggressive counterpart and its parental cell line, and (ii) the aggressive cell lines were each obtained from different host and their environment (human, rat, and mouse), though starting from the same parent cell line. Next, we developed a multi-step genomic pipeline that combines the DNA methylome profile with a chromosome cluster-oriented analysis. A total of 229 differentially hypermethylated genes were commonly found in the aggressive cell lines. Genome localization analysis revealed hypermethylation peaks and clusters, identifying eight hypermethylated gene promoters for validation in tissues from melanoma patients. Five CpG identified in primary melanoma tissues were transformed into a DNA methylation score that can predict survival (Log-rank test, p=0.0008). This strategy is potentially universally applicable to other diseases involving DNA methylation alterations.

Data availability

Sequencing data have been deposited in GEO under accession code GSE155856R-scripts are available in Source Code 1 fileThe datasets supporting the conclusions of this article are included within the article and the following Supplementary files

The following data sets were generated

Article and author information

Author details

  1. Arnaud Carrier

    Unité de Service et de Recherche USR 3388, CNRS-Pierre Fabre, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Cécile Desjobert

    Unité de Service et de Recherche USR 3388, CNRS-Pierre Fabre, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Loic Ponger

    CNRS UMR 7196, INSERM U1154, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Laurence Lamant

    Cancer Research Center of Toulouse, UMR 1037, INSERM, Université Toulouse III Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Matias Bustos

    Department of Translational Molecular Medicine, Providence Saint John's Health Center, Santa Monica, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jorge Torres-Ferreira

    Cancer Biology and Epigenetics Group, Portuguese Oncology Institute, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  7. Rui Henrique

    Cancer Biology and Epigenetics Group, Portuguese Oncology Institute, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  8. Carmen Jeronimo

    Cancer Biology and Epigenetics Group, Portuguese Oncology Institute, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  9. Luisa Lanfrancone

    Department of Experimental Oncology, Instituto Europeo di Oncologia, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  10. Audrey Delmas

    Cancer Research Center of Toulouse, UMR 1037, INSERM, Université Toulouse III Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Gilles Favre

    Cancer Research Center of Toulouse, UMR 1037, INSERM, Université Toulouse III Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Antoine Delaunay

    Laboratory for Functional Genomics, Fondation Jean Dausset-CEPH, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Florence Busato

    Laboratory for Epigenetics and Environment, CNRS, CEA-Institut de Biologie François Jacob, Evry, France
    Competing interests
    The authors declare that no competing interests exist.
  14. Dave SB Hoon

    Department of Translational Molecular Medicine, Providence Saint John's Health Center, Santa Monica, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Jorg Tost

    Laboratory for Epigenetics and Environment, CNRS, CEA-Institut de Biologie François Jacob, Evry, France
    Competing interests
    The authors declare that no competing interests exist.
  16. Chantal Etievant

    Unité de Service et de Recherche USR 3388, CNRS-Pierre Fabre, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  17. Joëlle Riond

    Unité de Service et de Recherche USR 3388, CNRS-Pierre Fabre, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  18. Paola B Arimondo

    Department Structural Biology and Chemistry, Institut Pasteur, CNRS UMR 3523, Paris, France
    For correspondence
    paola.arimondo@cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5175-4396

Funding

CNRS (ATIP to PBA)

  • Paola B Arimondo

Region Midi Pyrenees-CNRS (Equipe d'excellence to PBA)

  • Paola B Arimondo

Region Midi Pyrenees - CNRS (FEDER to PBA)

  • Paola B Arimondo

Fondation InnaBioSante (EpAM to PBA)

  • Paola B Arimondo

Adelson Medical Research Foundation (grant to DH and MB)

  • Dave SB Hoon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Tumour samples from melanoma patients were obtained from the tumour tissue bank at the Department of Pathology, IUCT-O Toulouse Hospital (France). The study was carried out in accordance with the institutional review board-approved protocols (CRB, AC-2013-1955) and the procedures followed were in accordance with the Helsinki Declaration.This study was approved by the institutional ethics committee of IPO Porto (CES-IPOP-FG13/2016).

Reviewing Editor

  1. C Daniela Robles-Espinoza, International Laboratory for Human Genome Research, Mexico

Publication history

  1. Received: March 11, 2022
  2. Accepted: September 18, 2022
  3. Accepted Manuscript published: September 20, 2022 (version 1)

Copyright

© 2022, Carrier et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Arnaud Carrier
  2. Cécile Desjobert
  3. Loic Ponger
  4. Laurence Lamant
  5. Matias Bustos
  6. Jorge Torres-Ferreira
  7. Rui Henrique
  8. Carmen Jeronimo
  9. Luisa Lanfrancone
  10. Audrey Delmas
  11. Gilles Favre
  12. Antoine Delaunay
  13. Florence Busato
  14. Dave SB Hoon
  15. Jorg Tost
  16. Chantal Etievant
  17. Joëlle Riond
  18. Paola B Arimondo
(2022)
DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness
eLife 11:e78587.
https://doi.org/10.7554/eLife.78587

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