Somatic copy number amplification and activating somatic mutations of EZH2 Y641 drive melanoma by epigenetic remodeling.

Hersey, Peter; Tiffen, Jessamy; Gallagher, Stuart J.; Filipp, Fabian V.

doi:10.1200/jco.2015.33.15_suppl.e22072

Cited by 1 publication

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“…These are the tumors characterized by overexpression of PRC2 encoding genes or by GOF mutations in the EZH2 gene leading to an increased PRC2 catalytic activity [2,19,20]. Amplification of the EZH2 coding region has been detected in different tumors [37][38][39][40]. Similarly, the SUZ12 gene is amplified in several tumors [41], nevertheless, there is a lack of information regarding the SUZ12 and EED amplification.…”

Section: Analysis Of Ezh2 Suz12 and Eed Dna Alterations In Patients' Samplesmentioning

confidence: 99%

Clinical Correlations of Polycomb Repressive Complex 2 in Different Tumor Types

Erokhin

Четверина

Győrffy

et al. 2021

Cancers

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PRC2 (Polycomb repressive complex 2) is an evolutionarily conserved protein complex required to maintain transcriptional repression. The core PRC2 complex includes EZH2, SUZ12, and EED proteins and methylates histone H3K27. PRC2 is known to contribute to carcinogenesis and several small molecule inhibitors targeting PRC2 have been developed. The present study aimed to identify the cancer types in which PRC2 targeting drugs could be beneficial. We queried genomic and transcriptomic (cBioPortal, KMplot) database portals of clinical tumor samples to evaluate clinical correlations of PRC2 subunit genes. EZH2, SUZ12, and EED gene amplification was most frequently found in prostate cancer, whereas lymphoid malignancies (DLBCL) frequently showed EZH2 mutations. In both cases, PRC2 alterations were associated with poor prognosis. Moreover, higher expression of PRC2 subunits was correlated with poor survival in renal and liver cancers as well as gliomas. Finally, we generated a Python application to analyze the correlation of EZH2/SUZ12/EED gene knockouts by CRISPR with the alterations detected in the cancer cell lines using DepMap data. As a result, we were able to identify mutations that correlated significantly with tumor cell sensitivity to PRC2 knockout, including SWI/SNF, COMPASS/COMPASS-like subunits and BCL2, warranting the investigation of these genes as potential markers of sensitivity to PRC2-targeting drugs.

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