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Your guide to studying histone H3 mutations in cancer.
Updated November 21, 2022
We've put together a quick overview of the most common histone mutations affecting histone 3 (H3) - H3K27M, H3K36M, H3G34 (W/V/R) - so you can easily find the right tools to study your histone mutant.
Contents
Recurrent histone mutations have been recently described in various cancer types, including brain tumors, chondroblastoma, giant cell tumors of bone, and leukemia. Current research suggests that histone mutations alter the epigenetic landscape, but underlying mechanisms are not completely understood.
The identification of widespread recurrent driver mutations in histones has raised significant interest in the development of novel targeted epigenetic therapies for histone mutant tumors, as well as biomarkers for diagnostics and monitoring of drug response.
Here we review the five common histone mutations affecting H3 - H3K27M, H3K36M, and H3G34 (W/V/R) (Figure 1) - and recommend our best recombinant monoclonal antibodies to study these targets.
H3K27M | |
IHC of paraffin-embedded mouse brain tissue labeling H3K27M with ab190631 at 1/500 dilution followed by Discovery UltraMap anti-rabbit (HRP). | H3K27M mutations are found in pediatric brain tumors and adult cancers, such as acute myeloid leukemia, melanoma, and glioma1. H3K27M acts as a suppressor of the PCR2 complex, leading to a global reduction of H3K27 di- and trimethylation levels (H3K27me2 and H3K27me3)2. We recommend Recombinant anti-H3K27M antibody - ChIP Grade (ab190631) Applications: WB, Indirect ELISA, IHC-P, ICC/IF, IP, ChIP Related targets: EZH2, SUZ12, EED, p53, PDFRA, FGFR1, ACVR1, BCOR, H3K27me2, H3K27me3 |
H3K36M | |
IHC of paraffin-embedded human chondroblastoma tissue labeling H3K36M with ab256384 at 1/4000 dilution followed by a goat anti-rabbit IgG H&L (HRP). | H3K36M is a potential oncogenic driver mutation in chondroblastomas; also found in pediatric soft tissue sarcomas and HNSCC. Similar to H3K27M, the H3K36M mutation suppresses the methyltransferase activity of SETD2 and NSD family proteins and leads to the global reduction of H3K36 di- and trimethylation levels3. We recommend Recombinant anti-H3K36M antibody (ab256384) Applications: IP, WB, IHC-P, ICC/IF, Flow Cyt, Indirect ELISA. Related targets: SETD2, NSD1, NSD2, H3K36me2, H3K36me3. |
Histone mutations at H3G34 include substitutions of glycine 34 with tryptophan (G34W), arginine (G34R), or valine (G34V). Several studies indicate that the replacement of H3G34 with any other amino acid residue blocks SETD2 binding and thereby may hinder the methylation of H3K361.