Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (stPNET) are pediatric embryonic brain tumors, which arise in a brain that is in the process of growth and development. They differ significantly from adult lesions and may involve unique genetic and epigenetic factors. However, the pathogenesis of these tumors is still elusive. My project consisted of four parts, investigating major genetic and epigenetic alterations of these tumors. / Multiple genetic studies have shown high frequency of loss (30--60%) on chromosome 8p in MBs. Microcell-mediated transfer of chromosome 8 suppressed tumorigenesis or the proliferation of colon and breast cancer cell, indicating that chromosome 8p is likely to include several TSGs in human cancers. In previous studies from our laboratory, results showed the frequency of loss on chromosome 8p is also rather high (66.7%). An overlapping HD region was identified in a 1.8cM interval on 8p22-23.1, between markers D8S520 and D8S1130, in two MBs (Yin et al., 2002), indicating that several candidate TSGs are located within or near this region. PinX1 on 8p23.1, a potential inhibitor of telomerase, is most likely the candidate TSG in MBs due to its location and function. To evaluate the genetic alterations of PinX1 and to investigate its role in MBs, the first part of my study is to perform mutation analysis in a series of 52 primary MBs, 3 MB cell lines and 4 primary stPNETs. Transcript expression of PinX1 was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in microdissected tumors and normal cerebellum. Using the telomeric repeat amplification protocol (TRAP) assay, 19 MBs, 2 stPNETs and all 3 MB cell lines were analyzed for telomerase activity. No somatic point mutations and loss of expression of PinX1 were detected in our series, suggesting that PinX1 is not the target gene on 8p23.1 in MBs. Although we did not find a significant association between PinX1 expression and telomerase activity, the presence of telomerase activity in 16 of 22 MBs and 1 of 2 stPNETs indicate that telomerase activation is associated with the development of this malignant disease. Our study represents the largest series of MB examined by telomerase repeat amplification protocol (TRAP) assay. (Abstract shortened by UMI.) / Chang Qing. / "April 2005." / Adviser: Ho-Keung Ng. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0191. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 201-228). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343621 |
| Date | January 2005 |
| Contributors | Chang, Qing., Chinese University of Hong Kong Graduate School. Division of Anatomical & Cellular Pathology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xxiii, 228 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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