ATRS Glioma Marker White Paper

The protein encoded by the ATRX gene belongs to a chromatin-remodeling path- way (H3.3-ATRX-DAXX) and is required for the incorporation of H3.3 in chromatin.

Mutations in this gene are associated with diverse changes in pattern of DNA methylation, chromosome congression during mitosis, and segregation in meio- sis as well as telomere dysfunction1

These changes may provide a link be- tween chromatin remodeling, DNA meth- ylation, and gene expression in develop- mental processes [provided by RefSeq, Jul 2017]. Phenotypically, the mutations result in several characteristic develop- mental abnormalities such as mental retardation, facial dysmorphism and al- pha-thalassemia (ATRX) syndrome1.

Figure 1: A. Immunohistochemical staining of human glioma tissue using HPA001906 shows strong nuclear im- munoreactivity in cancer cells. B. Western blot analysis in A-549 cells transfected with control siRNA, target specific siRNA probe #1 and #2, using Anti-ATRX antibody. Remaining relative intensity is presented. Loading control: Anti-GAPDH.

Figure 2: A. Immunohistochemical staining of human brain (high grade glioma) using AMAb90784 shows strong nuclear immunore- activity in cancer cells. B. Immunofluorescence staining in HeLa cell line with AMAb90784 shows clear nuclear (without nucleoli) staining in green. Microtubule probe is visualized in red. C.  Western blot analysis in A-549 cells transfected with control siRNA, target specific siRNA probe #1 and #2, using Anti-ATRX antibody. Remaining relative intensity is presented. Loading control: Anti-GAPDH.

ATRX, a marker for glioma

Around 2012, several research groups worldwide started to study the potential link between ATRX and glioma.

In this paper1 the authors summarized the recent studies and the correlations that had been made between different markers such as IDH1, p53, 1p/19q and ATRX with different types of glioma.

Figure 3: Multiplexed IHC-IF staining of glioblastoma multiforme (A) and oligodendroglioma (B) shows ATRX (red) and IDH1 (green) immunoreactivity in tumor cells using Anti-ATRX antibody (A: HPA001906, B: AMAb90784) and Anti-IDH1 antibody (AMAb90578). Nuclei are counterstained with DAPI.

Figure 4: Multiplexed IHC-IF staining of glioblastoma multiforme (A), astrocytoma (B) and oligodendroglioma (C) shows ATRX (nuclear, red) and GFAP (cytoplasmic, green) immunoreactivity in tumor cells using Anti-ATRX antibody (AMAb90784) and Anti-GFAP antibody (AMAb91033). Nuclei are counterstained with DAPI.

The paper concluded that depending on mutations in IDH1, 1p/19q and ATRX, gliomas could be classified into three groups:

  • Molecular Astrocytomas
  • Molecular Oligodendrogliomas
  • Molecular Glioblastomas

ATRX has now become a routine marker for classification of gliomas and is most often used in combination with various other markers such as IDH11-7, P532,3,4,7, PARP13, GFAP6, KI-672 and EGFR2.

The images below show examples of immunohistochemical stainings of select cases of glioblastomas, astrocytomas and oligodendrogliomas using antibodies for ATRX, IDH1 and GFAP.

Suggested Products

ANTI-ATRX AMAb90784

ANTI-ATRX AMAb90784

  • Application: IHC, WB*, ICC-IF
  • Sequence Identity Mouse/Rat: 96/97%

 

 

 

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ANTI-ATRX HPA001906

ANTI-ATRX HPA001906

  • Application: IHC*, WB*
  • Sequence Identity Mouse/Rat: 96/97%

 

 

 

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ANTI-ATRX HPA064684

ANTI-ATRX HPA064684

  • Application: ICC-IF
  • Sequence Identity Mouse/Rat: 51/57%

 

 

 

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ANTI-IDH1 AMAb90578

ANTI-IDH1 AMAb90578

  • Application: IHC, WB*, ICC-IF
  • Sequence Identity Mouse/Rat: 95/95%

 

 

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ANTI-IDH1 HPA035248

ANTI-IDH1 HPA035248

  • Application: IHC*, WB*
  • Sequence Identity Mouse/Rat: 95/95%

 

 

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ANTI-IDH1 HPA057936

ANTI-IDH1 HPA057936

  • Application: IHC*, WB*
  • Sequence Identity Mouse/Rat: 92/95%

 

 

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ANTI-GFAP AMAb91033

ANTI-GFAP AMAb91033

  • Application: IHC*, WB*
  • Sequence Identity Mouse/Rat: 98/100%

 

 

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ANTI-GFAP HPA063513

ANTI-GFAP HPA063513

  • Application: IHC*
  • Sequence Identity Mouse/Rat: 100/98%

 

 

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ANTI-GFAP HPA056030

ANTI-GFAP HPA056030

  • Application: IHC*, WB, ICC-IF
  • Sequence identity Mouse/Rat: 98/100%

 

 

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* Products with enhanced validation for indicated application

References

  1. Haberler C et al. Clinical Neuropathology practice news 2-2014: ATRX, a new candidate biomarker in gliomas. Clin Neuropathol 2014; 33(2):108-111.

  2. Oktay Y et al., IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation Sci Rep , 2016 Jun 10; 6:27569.

  3. Murnyák B et al. PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma
    Oncotarget , 2017 May 19; 8(28):46348-46362.

  4. Rosager AM et al. Expression and prognostic value of JAM-A in gliomas
    J Neurooncol , 2017 Jul 4; 135(1):107-117.

  5. Lee Y et al. The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas
    Acta Neuropathol Commun , 2017 Aug 29; 5:62.

  6. Valentini MC et al. Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma
    Oncotarget , 2017 Oct 4; 8(53):91636-91653.

  7. Li X et al. Primary Astrocytic Tumours and Paired Recur- rences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss
    Sci Rep , 2017 Oct 12; 7:13038.