Methylation and expression patterns of tropomyosin-related kinase genes in different grades of glioma.
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 p75(NTR) 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 < 0.05). No such significance was observed in other 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 < 0.05). Survival rate of HG patients with negative expressions of 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 p75(NTR) and the expression pattern of NTRK family in glioma as compared with the control samples (p < 0.05). There exists a correlation between the expression of 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.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.
Mahalakshmi
M
Palani
R
R
Arunkumar
Arrambakam Janardhanam
AJ
Vanisree
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics*; D020813:Receptor, trkB; D020812:Receptor, trkC / Q000096:biosynthesis / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; C484065:NGFR protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; C000591259:tropomyosin-related kinase-B, human