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Table of Contents    
COMMENTARY
Year : 2019  |  Volume : 67  |  Issue : 6  |  Page : 1498-1499

Loss of INI1 Expression-Understanding the Molecular Basis of Chordoid Meningiomas


1 Department of Pathology, Cytogenetic and Molecular Genetics Laboratory, Lab Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
2 Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication20-Dec-2019

Correspondence Address:
Dr. Meenakshi Tiwari
Department of Pathology, Lab Medicine, All India Institute of Medical Sciences, Patna - 801 507, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.273615

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How to cite this article:
Tiwari M, Saxena AK, Sharma LK. Loss of INI1 Expression-Understanding the Molecular Basis of Chordoid Meningiomas. Neurol India 2019;67:1498-9

How to cite this URL:
Tiwari M, Saxena AK, Sharma LK. Loss of INI1 Expression-Understanding the Molecular Basis of Chordoid Meningiomas. Neurol India [serial online] 2019 [cited 2020 Nov 26];67:1498-9. Available from: https://www.neurologyindia.com/text.asp?2019/67/6/1498/273615




We read with interest the article entitled “Loss of SMARCB1/INI1 Immunoexpression in Chordoid Meningiomas” by Malgulwar et al.[1] This study identifies for the first time the loss of integrase interactor 1 (INI1)/SMARCB1 expression in chordoid meningiomas as compared with other subtypes of meningiomas. The authors conducted the study in histopathologically confirmed cases of chordoid meningiomas (16 cases) in comparison with other subtypes of meningiomas (16 cases). In this study, 37.5% of cases of chordoid meningiomas (significantly high) showed a loss of INI1 immunoexpression, whereas other meningiomas retained the INI1 signal. Further, INI1 loss was associated with higher MIB-1L1. The authors also performed mutational analysis using Sanger sequencing in six cases of chordoid meningiomas but did not identify any pathological mutation. However, in four cases, nonpathogenic polymorphism in the SMARCB1 gene was identified. Genetic variation was identified in intron9 (C1119-41G>A) in four cases, exon7 (C897C>A) in three cases, and exon4 (c500+21T>A) in one case. Sequencing for AKT1E17K identified missense mutation only in one case, which too was associated with the loss of INI1 expression. Interestingly, this case had the highest MIB-1LI, a suggestive predisposition for aggressive behaviour.

INI1 genes located on chromosomal position 22q11.2.127 encode core subunit of SWI/SNF ATP-dependent chromatin remodeling complex involved in exposing nucleosome for transcription of DNA. INI1 abnormalities have been identified in a variety of atypical teratoid/rhabdoid tumors of the central nervous system (CNS), renal medullary carcinoma (RMC), epithelioid sarcoma, epithelioid malignant peripheral nerve sheath tumor (MPNST), myoepithelial carcinoma, and extraskeletal myxoid chondrosarcoma (EMCS).[2] As meningiomas are associated with nonrandom loss of chromosome 22 (Chr 22), INI1 located on the same chromosome becomes one of the genes of interest in meningiomas. In meningiomas, previous studies identified point mutation in exon 9 of the SMARCB1 gene in 4 of 126 cases.[3] Rieske et al. identified only one case out of the 80 samples of meningiomas that showed a cytosine insertion in codon 376.[4] Further, Bruder et al. did not identify inactivating mutations in any of the meningiomas cases.[5] Interestingly, in any of these studies, loss of INI1 expression was not observed in any meningiomas case.[3],[4],[5] The nonpathogenic polymorphism in the INI1 gene identified by authors coincides with the findings on rhabdoid tumors, where the loss of expression is observed in the absence of pathogenic mutations.[2] These studies indicate the involvement of epigenetic and posttranslational modifications in determining the INI1-associated pathogenesis of such tumors.

This study becomes very important as the understanding of the molecular basis of chordoid meningiomas is lacking. As a significantly high number of chordoid meningiomas cases demonstrated loss of INI1 expression, the present study forms the basis for the utility of loss of INI1 expression as a diagnostic and prognostic marker for such tumors. Moreover, the presence of high MIB-1 L1 in INI1 deficient chordoid meningiomas and presence of AKT1E17K mutation with INI1 loss of expression with the highest MIN-1 L1 value could be indicative of the aggressiveness of theses tumors and warrants long-term follow-up of such cases. Further, it is intriguing to understand the posttranslational events, interaction with other genes or proteins, and the factors that are inactivating INI1 gene expression in the absence of pathogenic mutations in such tumors. It will be an important step in understanding the pathogenesis of chordoid meningiomas and correlate with the aggressive behaviour of such tumors.



 
  References Top

1.
Malgulwar PB, Kakkar A, Sharma MC, Ghosh R, Pathak P, Sarkar C, et al. Loss of SMARCB1/INI1 immunoexpression in chordoid meningiomas. Neurology India 2019;67:1492-7.  Back to cited text no. 1
    
2.
Hollmann TJ, Hornick JL. INI1-deficient tumors: Diagnostic features and molecular genetics. Am J Surg Pathol 2011;35:e47-63.  Back to cited text no. 2
    
3.
Schmitz U, Mueller W, Weber M, Sévenet N, Delattre O, von Deimling A. INI1 mutations in meningiomas at a potential hotspot in exon 9. Br J Cancer 2001;84:199-201.  Back to cited text no. 3
    
4.
Rieske P, Zakrzewska M, Piaskowski S, Jaskólski D, Sikorska B, Papierz W, et al. Molecular heterogeneity of meningioma with INI1 mutation. Mol Pathol 2003;56:299-301.  Back to cited text no. 4
    
5.
Bruder CE, Dumanski JP, Kedra D. The mouse ortholog of the human SMARCB1 gene encodes two splice forms. Biochem Biophys Res Commun 1999;257:886-90.  Back to cited text no. 5
    




 

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