Somatic alterations and dysregulation of epigenetic modifiers in cancers Journal Article
| Authors: | Aumann, S.; Abdel-Wahab, O. |
| Article Title: | Somatic alterations and dysregulation of epigenetic modifiers in cancers |
| Abstract: | Genomic discovery efforts in patients with cancer have been critical in identifying a recurrent theme of mutations in epigenetic modifiers. A number of novel and exciting basic biological findings have come from this work including the discovery of an enzymatic pathway for DNA cytosine demethylation, a link between cancer metabolism and epigenetics, and the critical importance of post-translational modifications at specific histone residues in malignant transformation. Identification of cancer cell dependency on a number of these mutations has quickly resulted in the development of therapies targeting several of these genetic alterations. This includes, the development of mutant-selective IDH1 and IDH2 inhibitors, DOT1L inhibitors for MLL rearranged leukemias, EZH2 inhibitors for several cancer types, and the development of bromodomain inhibitors for many cancer types - all of which are in early phase clinical trials. In many cases, however, specific genetic targets linked to malignant transformation following mutations in individual epigenetic modifiers are not yet known. In this review we present functional evidence of how alterations in frequently mutated epigenetic modifiers promote malignant transformation and how these alterations are being targeted for cancer therapeutics. |
| Keywords: | leukemia; gene mutation; somatic mutation; nonhuman; drug targeting; neoplasm; metabolism; enzyme inhibitor; cancer therapy; dna methylation; protein processing; epigenetics; histone; cancer cell; malignant transformation; dna methyltransferase 3a; clinical trial (topic); e1a associated p300 protein; histone modification; cytosine; mixed lineage leukemia protein; asxl1; ezh2; bap1; dnmt3a; cyclic amp responsive element binding protein binding protein; polycomb repressive complex 2; isocitrate dehydrogenase 2; crebbp; ep300; human; article; bromodomain inhibitor |
| Journal Title: | Biochemical and Biophysical Research Communications |
| Volume: | 455 |
| Issue: | 1-2 |
| ISSN: | 0006-291X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2014-12-05 |
| Start Page: | 24 |
| End Page: | 34 |
| Language: | English |
| DOI: | 10.1016/j.bbrc.2014.08.004 |
| PROVIDER: | scopus |
| PUBMED: | 25111821 |
| PMCID: | PMC6630175 |
| DOI/URL: | |
| Notes: | Export Date: 2 January 2015 -- Source: Scopus |
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