American Association for Cancer Research
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00085472can181214-sup-200512_2_supp_5157682_p61n41.xlsx (206.75 kB)

Suppl Table S3 from TET2-Dependent Hydroxymethylome Plasticity Reduces Melanoma Initiation and Progression

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posted on 2023-03-31, 03:07 authored by Elise Bonvin, Enrico Radaelli, Martin Bizet, Flavie Luciani, Emilie Calonne, Pascale Putmans, David Nittner, Nitesh Kumar Singh, Sara Francesca Santagostino, Valérie Petit, Lionel Larue, Jean Christophe Marine, François Fuks

DhmR and gene expression tet-/- related to Fig3

Funding

Belgian Fonds de la Recherche Scientifique (FNRS)

ULB Foundation

NIH/NCI

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ARTICLE ABSTRACT

Although numerous epigenetic aberrancies accumulate in melanoma, their contribution to initiation and progression remain unclear. The epigenetic mark 5-hydroxymethylcytosine (5hmC), generated through TET-mediated DNA modification, is now referred to as the sixth base of DNA and has recently been reported as a potential biomarker for multiple types of cancer. Loss of 5hmC is an epigenetic hallmark of melanoma, but whether a decrease in 5hmc levels contributes directly to pathogenesis or whether it merely results from disease progression–associated epigenetic remodeling remains to be established. Here, we show that NRAS-driven melanomagenesis in mice is accompanied by an overall decrease in 5hmC and specific 5hmC gains in selected gene bodies. Strikingly, genetic ablation of Tet2 in mice cooperated with oncogenic NRASQ61K to promote melanoma initiation while suppressing specific gains in 5hmC. We conclude that TET2 acts as a barrier to melanoma initiation and progression, partly by promoting 5hmC gains in specific gene bodies. This work emphasizes the importance of epigenome plasticity in cancer development and highlights the involvement of druggable epigenetic factors in cancer.

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