Histone H3 mutant markers

Your guide to studying histone H3 mutations in cancer.

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.

Histone mutations in cancer​

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) - and recommend our best recombinant monoclonal antibodies to study these targets.

H3K27M

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.

Applications: WB, Indirect ELISA, IHC-P, ICC/IF, IP, ChIP

IHC of paraffin-embedded mouse brain tissue labeling H3K27M with ab190631 at 1/500 dilution followed by Discovery UltraMap anti-rabbit (HRP).

We recommend

Recombinant anti-H3K27M antibody - ChIP Grade (ab190631)

Browse all H3K27M products

References

View 2 references for H3K27M

H3K36M

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 levels1.

Applications: IP, WB, IHC-P, ICC/IF, Flow Cyt, Indirect ELISA.

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).

We recommend

Recombinant anti-H3K36M antibody (ab256384)

Browse all H3K36M products

References

View 1 reference for H3K36M

H3G34W

H3G34W mutation is a substitution of glycine 34 with tryptophan (G34W); it's a high-frequency mutation (>90%) in giant cell tumor of bone (GCTB).

In GCTB, H3.3G34W expression was shown to promote cellular proliferation  in-vitro  by inducing transcriptional deregulation and splicing alterations1.

Applications: ChIP, WB, ICC/IF, Flow Cyt, Dot blot, IHC-P.

We recommend

Recombinant anti-histone H3.3 (mutated G34W) antibody - ChIP Grade (ab272691)

References

View 1 reference for H3G34W

H3G34V

H3G34V mutation is a substitution of glycine 34 with valine (G34V). H3G34V/R mutations are predominantly found in high-grade gliomas of children and adolescents and are associated with loss-of-function mutations in  p53  and  ATRX,  as well as with the deregulated expression of N-Myc protein1.

Applications: WB, ICC/IF, Flow Cyt, Dot blot, ChIP, IHC-P.

IHC of paraffin-embedded human GCTB tissue labeling H3.3G34V with ab254401 at 1/1000 dilution (0.542 µg/mL) dilution followed by rabbit-specific IHC polymer detection kit HRP/DAB (ab209101).

We recommend

Recombinant anti-histone H3.3 (mutated G34V) antibody- ChIP Grade (ab254401)

References

View 1 reference for H3G34V

H3G34R

H34G34R mutation is a substitution of glycine 34 with arginine (G34R).

H3G34V/R mutations are predominantly found in high-grade gliomas and are associated with loss-of-function mutations in  p53  and  ATRX1.

IHC of paraffin-embedded human GCTB tissue labeling H3.3G34R with ab254402 at 1/2000 dilution followed by a rabbit-specific IHC polymer detection kit HRP/DAB (ab209101).

We recommend

Recombinant anti-histone H3.3 (mutated H3G34R) antibody - ChIP Grade (ab254402)

References

View 1 reference for H3G34R

References

H3K27M

Lowe, B. R., Maxham, L. A., Hamey, J. J., et al. Histone H3 mutations: an updated view of their role in chromatin deregulation and cancer. Cancers.  11  ,660 (2019)

Lewis, P. W., et al. Inhibition of PRC2 activity by a gain of function H3 mutation found in pediatric glioblastoma. Science  340  ,857–61 (2013)

H3K36M

Funato, K. & , Tabar, V. Histone mutations in cancer Annu. Rev. Cancer Biol.  2  (1),337-351 (2018)

H3G34W

Lim, J., et al. The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing. Sci. Rep.  7  ,13459 (2019)

H3G34V

Bjerke, L., et al. Histone H3.3 mutations drive pediatric glioblastoma through upregulation of MYCN. Cancer Discov.  3  ,512-519 (2013)

H3G34R

Bjerke, L., et al. Histone H3.3 mutations drive pediatric glioblastoma through upregulation of MYCN. Cancer Discov.  3  ,512-519 (2013)