1. DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness
- Author
-
Arnaud Carrier, Cécile Desjobert, Loic Ponger, Laurence Lamant, Matias Bustos, Jorge Torres-Ferreira, Rui Henrique, Carmen Jeronimo, Luisa Lanfrancone, Audrey Delmas, Gilles Favre, Antoine Daunay, Florence Busato, Dave SB Hoon, Jorg Tost, Chantal Etievant, Joëlle Riond, Paola B Arimondo, Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), PIERRE FABRE-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), PIERRE FABRE, Josep Carreras Leukaemia Research Institute (IJC), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular Oncology [Santa Monica, CA, USA] (Providence Saint John’s Health Center), John Wayne Cancer Institute [Santa Monica, CA, USA], Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), Universidade do Porto = University of Porto, European Institute of Oncology [Milan] (ESMO), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Riond, Joelle, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
chromosomes ,Guanine ,Skin Neoplasms ,oriented approach ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,chromosome clusters ,Chromosomes ,General Biochemistry, Genetics and Molecular Biology ,Epigenesis, Genetic ,Phosphates ,Cytosine ,Epigenome ,Mice ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,melanoma ,Animals ,Humans ,human ,Melanoma ,cancer biology ,DNA methylation ,General Immunology and Microbiology ,General Neuroscience ,General Medicine ,DNA Methylation ,[SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology ,Rats ,Gene Expression Regulation, Neoplastic ,epigenomics ,gene expression ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,CpG Islands ,patient outcome ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
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. 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.
- Published
- 2022