Analisis Gen Penindas Tumor P16 Dan Asai Aktiviti Telomerase Di Kalangan Pesakit Tumor Sistem Saraf Pusat Di Malaysia

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dc.contributor.authorSarina Sulong
dc.date.accessioned2016-11-21T07:02:37Z
dc.date.available2016-11-21T07:02:37Z
dc.date.issued2003-04
dc.description.abstractThe p16 gene is a tumour suppressor gene that encodes a negative regulator involved in regulating the cell cycle at the G}-S checkpoint. Both of p 16 gene (MTSlICDKN2NINK4a) inactivation and presence oftelomerase enzyme are proposed to be involved in tumourigenesis. Telomerase is an enzyme that stabilizes telomere length and may be useful as a tumour marker for malignancy. Its activity has been detected in germ line cells and most cancer cells, but not in most of the normal somatic cells. Our objectives are to investigate the possible p16 gene alterations via homozygous deletion and mutation analysis; and to detect telomerase activity in central nervous system tumours.ยท A total of 50 tumour tissues collected between 1997 to 2002 from the Brain Tumour Tissue Bank of Neuroscience Unit in USM were used in p16 gene analysis and 23 of these were also utilized in telomerase analysis. Homozygous deletion of p 16 gene was determined by the absence of PCR product of the gene while the GAPDH gene amplification was used as an internal control by multiplex- PCR analysis. PCR-SSCP (Single-Strand Conformation Polymorphism) analysis was performed to screen for p 16 gene mutation at exon I and 2, which was confirmed by DNA sequencing analysis. Telomerase activity was detected based on a PCR-Telomeric Repeat Amplification Protocol (TRAP) using a TRAPEZE Telomerase Detection Kit (Intergen, Co). The PCR products were electrophoresed on a 12% polyacrylamide gel and stained with silver staining. Positive amplification of p 16 gene and GAPDH gene were observed in all samples, suggested no homozygous deletion occurred. Mutation screening analysis of p 16 gene indicated that there was no mobility shift and suggested no mutation at exon 1 and 2 had occurred in all samples. DNA sequencing results on all high-grade tumours showed that all base sequences of exon I and 2 were normal. Telomerase activity was detected in 26.1 % of the tumour samples and mostly present in high-grade tumours (66.7%). There was a significant association (Fisher's exact test) between telomerase activity status with tumour grade (p=O.008). This activity was detected in the analysed tumours, supporting the fact that activation of telomerase is an important feature for tumourigenesis. However, alteration of the p16 gene was not identified in all the samples and suggested that the gene may not playa major role in tumourigenesis of these tumours in Malaysia. It is possible that there is another mechanism of p 16 gene inactivation involved in the development of these tumours such as hypermethylation of this gene in promoter region. This study indicates that there is no inactivation of p 16 gene, while there is a presence of te10merase activity among the central nervous system tumour's patients in Malaysia.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/3127
dc.subjectThe p16 gene is a tumour suppressor gene that encodes a negative regulatoren_US
dc.subjectinvolved in regulating the cell cycle at the G}-S checkpoint.en_US
dc.titleAnalisis Gen Penindas Tumor P16 Dan Asai Aktiviti Telomerase Di Kalangan Pesakit Tumor Sistem Saraf Pusat Di Malaysiaen_US
dc.typeThesisen_US
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