Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma

Yu, Mengxue; Qian, Kaiyu; Wang, Gang; Xiao, Yu; Zhu, Yuan; Ju, Lingao

doi:10.3389/fonc.2023.1114461

Cited by 2 publications

(3 citation statements)

References 117 publications

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“…Regarding SETD2, the HMT responsible of trimethylating H3K36, it is mutated in a range of tumor types, including 13% of cases in ccRCC [ 210 , 211 ]. Mechanistically, a study in ccRCC has described that the loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcriptional output through regulation of chromatin accessibility [ 132 ].…”

Section: Molecular Alterations In Cancer Metastasismentioning

confidence: 99%

Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics

Janin

Dávalos

Esteller

2023

Cancer Metastasis Rev

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Most of the cancer-associated mortality and morbidity can be attributed to metastasis. The role of epigenetic and epitranscriptomic alterations in cancer origin and progression has been extensively demonstrated during the last years. Both regulations share similar mechanisms driven by DNA or RNA modifiers, namely writers, readers, and erasers; enzymes responsible of respectively introducing, recognizing, or removing the epigenetic or epitranscriptomic modifications. Epigenetic regulation is achieved by DNA methylation, histone modifications, non-coding RNAs, chromatin accessibility, and enhancer reprogramming. In parallel, regulation at RNA level, named epitranscriptomic, is driven by a wide diversity of chemical modifications in mostly all RNA molecules. These two-layer regulatory mechanisms are finely controlled in normal tissue, and dysregulations are associated with every hallmark of human cancer. In this review, we provide an overview of the current state of knowledge regarding epigenetic and epitranscriptomic alterations governing tumor metastasis, and compare pathways regulated at DNA or RNA levels to shed light on a possible epi-crosstalk in cancer metastasis. A deeper understanding on these mechanisms could have important clinical implications for the prevention of advanced malignancies and the management of the disseminated diseases. Additionally, as these epi-alterations can potentially be reversed by small molecules or inhibitors against epi-modifiers, novel therapeutic alternatives could be envisioned.

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Section: Molecular Alterations In Cancer Metastasismentioning

confidence: 99%

Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics

Janin

Dávalos

Esteller

2023

Cancer Metastasis Rev

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“…Along with PBRM1 and BAP1, the SETD2 gene is located in the 3p chromosome. It is a histone-lysine N-methyltransferase that plays a role in transcription regulation and alternative splicing [54]. Its loss-of-function mutation has been observed to cause microsatellite instability [55,56].…”

Section: Setd2mentioning

confidence: 99%

“…Interestingly, its mutation is frequently associated with PBRM1 mutation, but the association of the two mutations has no greater impact on overall prognosis than the single PBRM1 mutation [57]. Its mutation is reported with a frequency of 13-30% in different case series [54]. SETD2 loss of function is usually subclonal, meaning that it is only present in some cells within a single tumor [58].…”

Section: Setd2mentioning

confidence: 99%

Genomic Profiling and Molecular Characterization of Clear Cell Renal Cell Carcinoma

Pezzicoli,

Ciciriello,

Musci

et al. 2023

Current Oncology

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Clear cell renal cell carcinoma (ccRCC) treatment has undergone three major paradigm shifts in recent years, first with the introduction of molecular targeted therapies, then with immune checkpoint inhibitors, and, more recently, with immune-based combinations. However, to date, molecular predictors of response to targeted agents have not been identified for ccRCC. The WHO 2022 classification of renal neoplasms introduced the molecularly defined RCC class, which is a first step in the direction of a better molecular profiling of RCC. We reviewed the literature data on known genomic alterations of clinical interest in ccRCC, discussing their prognostic and predictive role. In particular, we explored the role of VHL, mTOR, chromatin modulators, DNA repair genes, cyclin-dependent kinases, and tumor mutation burden. RCC is a tumor whose pivotal genomic alterations have pleiotropic effects, and the interplay of these effects determines the tumor phenotype and its clinical behavior. Therefore, it is difficult to find a single genomic predictive factor, but it is more likely to identify a signature of gene alterations that could impact prognosis and response to specific treatment. To accomplish this task, the interpolation of large amounts of clinical and genomic data is needed. Nevertheless, genomic profiling has the potential to change real-world clinical practice settings.

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Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma

Cited by 2 publications

References 117 publications

Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics

Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics

Genomic Profiling and Molecular Characterization of Clear Cell Renal Cell Carcinoma

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