DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness
Carrier, Arnaud (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Desjobert, Cécile (Unité de Service et de Recherche)
Ponger, Loic (Sorbone University)
Lamant, Laurence (Université Toulouse III Paul Sabatier)
Bustos, Matias (Saint John's Cancer Institute)
Torres Ferreira, Jorge (Portuguese Oncology Institute of Porto)
Henrique, Rui (University of Porto)
Jeronimo, Carmen (University of Porto)
Lanfrancone, Luisa (Instituto Europeo di Oncologia)
Delmas, Audrey (Université Toulouse III Paul Sabatier)
Favre, Gilles (Université Toulouse III Paul Sabatier)
Daunay, Antoine (Fondation Jean Dausset-CEPH)
Busato, Florence (Université Paris-Saclay. Centre National de Recherche en Génomique Humaine)
Hoon, Dave S. B. (Saint John's Cancer Institute)
Tost, Jorg (Université Paris-Saclay. Centre National de Recherche en Génomique Humaine)
Etievant, Chantal (Unité de Service et de Recherche)
Riond, Joëlle (Université Toulouse III Paul Sabatier)
Arimondo, Paola Barbara (Institut Pasteur)

Data:	2022
Resum:	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 was 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 Cytosine-phosphate-Guanine (CpGs) 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.
Nota:	Funder Grant reference number Author Centre National de la Recherche Scientifique Centre National de la Recherche Scientifique Centre National de la Recherche Scientifique ATIP Region Midi Pyrenees-Equipe d'excellence Region Midi Pyrenees-FEDER Paola B Arimondo Paola B Arimondo Paola B Arimondo Fondation InnaBioSante EpAM Paola B Arimondo Adelson Medical Research Foundation Dave SB Hoon Matias Bustos The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Animals ; Chromosomes ; CpG Islands ; Cytosine ; DNA Methylation ; Epigenesis, Genetic ; Epigenome ; Gene Expression Regulation, Neoplastic ; Guanine ; Humans ; Melanoma ; Mice ; Phosphates ; Rats ; Skin Neoplasms
Publicat a:	eLife, Vol. 11 (september 2022) , p. e78587, ISSN 2050-084X

DOI: 10.7554/eLife.78587
PMID: 36125262

19 p, 964.7 KB

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