Loss of 5-Hydroxymethylcytosine Is an Epigenetic Hallmark of Melanoma
نویسندگان
چکیده
DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma epigenome. We show that downregulation of isocitrate dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.
منابع مشابه
Loss of the epigenetic mark, 5-Hydroxymethylcytosine, correlates with small cell/nevoid subpopulations and assists in microstaging of human melanoma
Melanomas in the vertical growth phase (VGP) not infrequently demonstrate cellular heterogeneity. One commonly encountered subpopulation displays small cell/nevoid morphology. Although its significance remains unknown, such subpopulations may pose diagnostic issues when faced with differentiating such changes from associated nevus or mistaking such regions for nevic maturation (pseudomaturation...
متن کاملEpigenetic Dysregulation in Cutaneous Malignant Melanoma: Advancing Approaches to Diagnosis, Prognosis, and Therapeutic Targeting
................................................................................................................................... 1 LIST OF ABBREVIATIONS ......................................................................................................... 4 BACKGROUND AND INTRODUCTION ................................................................................... 5 The ‘black cancer’:...
متن کاملEpigenetic Dysregulation in Cutaneous Malignant Melanoma: Advancing Approaches to Diagnosis, Prognosis, and Therapeutic Targeting
................................................................................................................................... 1 LIST OF ABBREVIATIONS ......................................................................................................... 4 BACKGROUND AND INTRODUCTION ................................................................................... 5 The ‘black cancer’:...
متن کاملEpigenetic Dysregulation in Cutaneous Malignant Melanoma: Advancing Approaches to Diagnosis, Prognosis, and Therapeutic Targeting
................................................................................................................................... 1 LIST OF ABBREVIATIONS ......................................................................................................... 4 BACKGROUND AND INTRODUCTION ................................................................................... 5 The ‘black cancer’:...
متن کاملEpigenetic Dysregulation in Cutaneous Malignant Melanoma: Advancing Approaches to Diagnosis, Prognosis, and Therapeutic Targeting
................................................................................................................................... 1 LIST OF ABBREVIATIONS ......................................................................................................... 4 BACKGROUND AND INTRODUCTION ................................................................................... 5 The ‘black cancer’:...
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ورودعنوان ژورنال:
- Cell
دوره 150 شماره
صفحات -
تاریخ انتشار 2012