Methylation and Expression Patterns of Tropomyosin-Related Kinase Genes in Different Grades of Glioma

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• 作者：Mahalakshmi Palani (1)
  R. Arunkumar (2)
  Arrambakam Janardhanam Vanisree (1)
  
• 关键词：Glioma ; Tropomyosin ; related kinases ; Promoter methylation ; Neurotrophin receptor
• 刊名：NeuroMolecular Medicine
• 出版年：2014
• 出版时间：September 2014
• 年：2014
• 卷：16
• 期：3
• 页码：529-539
• 全文大小：1,175 KB
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• 作者单位：Mahalakshmi Palani (1)
  R. Arunkumar (2)
  Arrambakam Janardhanam Vanisree (1)
  
  1. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India
  2. Department of Neurology and Neurosurgery, Madras Medical College, Chennai, Tamil Nadu, India
  
• ISSN：1559-1174

文摘

Tropomyosin-related kinase family (NTRK1, NTRK2 and NTRK3) is well known to play an important role in the pathogenesis of brain tumour, which exhibit heterogeneity in its biological and clinical behaviour. However, the mechanism that regulates NTRKs in glioma is not well understood. The present study investigates the epigenetic status (methylation) of NTRKs and their expression in different grades of glioma. Promoter methylation and structural relationship of NTRKs was assessed using methylation-specific PCR followed by chromatin immunoprecipitation in brain tissue samples from 220 subjects with different grades of glioma. Control brain samples were also assessed similarly. Reverse transcriptase PCR was performed to analyse the expressions of NTRK mRNAs in the grades of glioma. In addition, the expression level of p75NTR protein was analysed using immunofluorescent technique in all of the samples. The overall percentage of NTRK3 gene methylation frequency with subsequent loss of mRNA expression was significantly higher in glioma compared with control samples (p?NTRK1 and NTRK2 genes. Further, mRNA expression pattern of NTRK1 and NTRK2 genes was found to be significantly higher in low grades as compared with high grades (HG) and control samples (p?NTRK1 and NTRK2 was poor than those with the positive expressions of both NTRK1 and NTRK2. Further, a significant correlation was observed with reduced expression of p75NTR and the expression pattern of NTRK family in glioma as compared with the control samples (p?NTRK family and different grades of glioma with a significant suggestion that the promoter methylation does not play role in the regulation of these genes in glioma. Further, poor survival could be associated with NTRK mRNAs 1 and 2. Hence, NTRKs are potential probes for assessing the behaviour of different grades of glioma, which could also function as significant prognostic factors and thus deserve wider attention for an effective management of the grades.