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. 2017 Mar;27(2):138-145.
doi: 10.1111/bpa.12364. Epub 2016 Jun 13.

ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset

Suvendu Purkait  1 , Christopher A Miller  2 , Anupam Kumar  1 , Vikas Sharma  1 , Pankaj Pathak  1 , Prerana Jha  1 , Mehar Chand Sharma  1 , Vaishali Suri  1 , Ashish Suri  3 , B S Sharma  3 , Robert S Fulton  2 , Shashank Sharad Kale  3 , Sonika Dahiya  4 , Chitra Sarkar  1
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ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset

Suvendu Purkait et al. Brain Pathol. 2017 Mar.

VSports - Abstract

This study aims (1) to evaluate ATRX expression in different grades and subtypes of gliomas and correlate with other hallmark genetic alterations, (2) to identify and characterize mosaic/heterogeneous staining in gliomas in terms of mutation status. One hundred seventy six cases of glioma were assessed for ATRX immunohistochemistry and subdivided into positive, negative and mosaic/heterogeneous staining patterns. Five cases with heterogeneous staining were further subjected to next generation sequencing. Higher frequency of ATRX immune-negativity was detected in grade II/III astrocytic, oligoastrocytic tumors and secondary glioblastomas (GBMs), while infrequent in primary GBMs and rare in oligodendrogliomas. Loss of expression was significantly associated with IDH1 and/or TP53 mutation, while mutually exclusive with 1p/19q codeletion. Mosaic/heterogeneous staining was detected exclusively in GBMs (21. 2%) VSports手机版. Two different types of mosaic staining were identified (1) Admixture of positive and negative nuclei or intermixed mosaic and (2) Separate fragments with positive and negative/intermixed mosaic staining. ATRX mutation was identified in 2/5 (40%) cases with mosaic staining while one case showed DAXX mutation. All these cases were characterized by distinctly separate immune-negative and positive/intermixed foci. Hence, it is suggested that cases with heterogeneous staining (especially those with distinctly negative fragments) should be subjected to mutation analysis. .

Keywords: ATRX; Glioma; heterogeneous staining; mosaic staining. V体育安卓版.

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Figures

Figure 1
Figure 1
Representative photomicrographs of ATRX immunostaining in cases subjected to sequencing [arrow—endothelial positivity in negatively stained areas/cases (internal control)] with the corresponding ATRX sequencing results.
Figure 2
Figure 2
Correlation of different ATRX staining pattern with key molecular genetic alterations (EGFR amplification, PDGFRA amplification, TP53 mutation, IDH‐1 mutation and NF1 alteration) in GBMs.
Figure 3
Figure 3
Representative photographs showing ATRX ( A,B ) and DAXX ( C ) mutations Red reads mapped to forward strand and Blue mapped to reverse strand. Bases that differ from the reference are displayed with their letters in color. A. ATRX mutation—Frameshift variant ENSP00000362441.4:p.Lys1045Ter. B. ATRX mutation‐ Stop gain‐ and splice region variant ENSP00000362441.4:p.Ser1245Ter. C. DAXX mutation—Missense variant NSP00000363668.5:p.Asp331Asn.
See this image and copyright information in PMC

V体育官网入口 - References

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