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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 醫學檢驗暨生物技術學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42874
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor林亮音
dc.contributor.authorI-Hsien Chienen
dc.contributor.author簡意軒zh_TW
dc.date.accessioned2021-06-15T01:27:01Z-
dc.date.available2009-09-15
dc.date.copyright2009-09-15
dc.date.issued2009
dc.date.submitted2009-07-22
dc.identifier.citation1. Hartkamp J, Roberts SG: The role of the Wilms' tumour-suppressor protein WT1 in apoptosis. Biochem Soc Trans 2008, 36(Pt 4):629-631.
2. Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE: Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci U S A 1991, 88(21):9618-9622.
3. Yang L, Han Y, Suarez Saiz F, Minden MD: A tumor suppressor and oncogene: the WT1 story. Leukemia 2007, 21(5):868-876.
4. Han Y, San-Marina S, Liu J, Minden MD: Transcriptional activation of c-myc proto-oncogene by WT1 protein. Oncogene 2004, 23(41):6933-6941.
5. Hewitt SM, Hamada S, McDonnell TJ, Rauscher III FJ,Saunders GF. Regulation of the proto-oncogenes bcl-2 and cmyc by the Wilms’ tumor suppressor gene WT1. Cancer Res 1995; 55: 5386–5389.
6. Heckman C, Mochon E, Arcinas M, Boxer LM. The WT1 protein is a negative regulator of the normal bcl-2 allele in t(14;18) lymphomas. J Biol Chem 1997; 272: 19609–19614.
7. Little MH, Williamson KA, Mannens M, Kelsey A, Gosden C,Hastie ND et al. Evidence that WT1 mutations in Denys–Drash syndrome patients may act in a dominant-negative fashion. Hum Mol Genet 1993; 2: 259–264.
8. Little M, Holmes G, Bickmore W, van H, Hastie V N,Wainwright B. DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. Hum Mol Genet 1995; 4: 351–358.
9. Hosen N, Sonoda Y, Oji Y, Kimura T, Minamiguchi H, Tamaki H et al. Very low frequencies of human normal CD34+ haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol 2002;116: 409–420.
10. Baird PN, Simmons PJ. Expression of the Wilms’ tumor gene (WT1) in normal hemopoiesis. Exp Hematol 1997; 25: 312–320.
11. Miyagi T, Ahuja H, Kubota T, Kubonishi I, Koeffler HP, Miyoshi I. Expression of the candidate Wilm’s tumor gene, WT1, in human leukemia cells. Leukemia 1993; 7: 970–977.
12. Miwa H, Beran M, Saunders GF. Expression of the Wilms’ tumor gene (WT1) in human leukemias. Leukemia 1992; 6: 405–409.
13. Nishida S, Hosen N, Shirakata T, Kanato K, Yanagihara M, Nakatsuka S et al. AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1. Blood 2006; 107: 3303–3312.
14. Miwa H, Beran M, Saunders GF. Expression of the Wilms’ tumor gene (WT1) in human leukemias. Leukemia 1992; 6: 405–409.
15. Menssen HD, Renkl HJ, Rodeck U, Maurer J, Notter M, Schwartz S et al. Presence of Wilms’ tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia 1995; 9: 1060–1067.
16. Chiusa L, Francia di Celle P, Campisi P, Ceretto C, Marmont F, Pich A. Prognostic value of quantitative analysis of WT1 gene transcripts in adult acute lymphoblastic leukemia. Haematologica 2006; 91: 270–271.
17. Tamaki H, Ogawa H, Ohyashiki K, Ohyashiki JH, Iwama H, Inoue K et al. The Wilms’ tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. Leukemia 1999; 13: 393–399.
18. Ellisen LW, Carlesso N, Cheng T, Scadden DT, Haber DA. The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO J 2001; 20: 1897–1909.
19. Svedberg H, Richter J, Gullberg U. Forced expression of the Wilms tumor 1 (WT1) gene inhibits proliferation of human hematopoietic CD34(+) progenitor cells. Leukemia 2001; 15: 1914–1922.
20. Svensson E, Eriksson H, Gekas C, Olofsson T, Richter J, Gullberg U. DNA-binding dependent and independent functions of WT1 protein during human hematopoiesis. Exp Cell Res 2005; 308: 211–221.
21. King-Underwood L, Renshaw J, Pritchard-Jones K. Mutations in the Wilms’ tumor gene WT1 in leukemias. Blood 1996; 87: 2171–2179.
22. Valk PJ, Verhaak RG, Beijen MA, Erpelinck CA, Barjesteh van Waalwijk van Doorn-Khosrovani S, Boer JM et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. New Engl J Med 2004; 350: 1617–1628.
23. Smith SI, Down M, Boyd AW, Li CL. Expression of the Wilms’ tumor suppressor gene, WT1, reduces the tumorigenicity of the leukemic cell line M1 in C.B-17 scid/scid mice. Cancer Res 2000; 60: 808–814.
24. Ririe KM, Rasmussen RP, Wittwer CT: Product differentiation by analysis
of DNA melting curves during the polymerase chain reaction. Anal Biochem 1997, 245:154–160
25. Wittwer CT, Ririe KM, Andrew RV, David DA, Gundry RA, Balis UJ: The LightCycler: a microvolume multisample fluorimeter with rapid temperature control. Biotechniques 1997, 22:176–181
26. Haukur Gudnason1, Martin Dufva, D.D. Bang and Anders Wolff,*: Comparison of multiple DNA dyes for real-time PCR: effects of dye concentration and sequence composition on DNA amplification and melting temperature.Nucleic Acids Research, 2007, Vol. 35, No. 19
27. Robert Slinger, Deana Bellfoy, Marc Desjardins, Francis Chan: High-resolution melting assay for the detection of gyrA mutations causing quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi. Diagnostic Microbiology and Infectious Disease ,2007 ,455–458
28. Wittwer CT, Reed GH, Gundry CN, Vandersteen JG, Pryor RJ: High resolution
genotyping by amplicon melting analysis using LCGreen. Clin Chem 2003, 49:853–860
29. Liew M, Pryor R, Palais R, Meadows C, Erali M, Lyon E, Wittwer C: Genotyping of single-nucleotide polymorphisms by high-resolution melting of small amplicons. Clin Chem 2004, 50:1156–1164
30. Willmore-Payne C, Holden JA, Tripp S, Layfield LJ: Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol 2005, 36:486-493.
31. Willmore-Payne C, Holden JA, Layfield LJ: Detection of epidermal growth factor receptor and human epidermal growth factor receptor 2 activating mutations in lung adenocarcinoma by high-resolution melting amplicon analysis: correlation with gene copy number, protein expression, and hormone receptor expression. Hum Pathol 2006, 37:755-763.
32. Nomoto K, Tsuta K, Takano T, Fukui T, Fukui T, Yokozawa K,Sakamoto H, Y oshida T, Maeshima AM, Shibata T, Furuta K, Ohe Y,Matsuno Y: Detection of EGFR mutations in archived cytologic specimens of non-small cell lung cancer using high-resolution melting analysis. Am J Clin Pathol 2006, 126:608-615.
33. Krypuy M, Newnham GM, Thomas DM, Conron M, Dobrovic A: High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer. BMC Cancer 2006, 6:295.
34. AM Willasch1, B Gruhn2, T Coliva3: Standardization of WT1 mRNA quantitation for minimal residual disease monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study. Leukemia ,2009, 1–8
35. Marie-Pierre Audrezet, Aure´ lia Dabricot,Ce´ dric Le Marechal, and Claude Ferec : Validation of High-Resolution DNA Melting Analysis for Mutation Scanning of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene. Journal of Molecular Diagnostics 2008,10,424-434.
36. Martin Pichler, Marija Balic, Elke Stadelmeyer,Christoph Ausch, Martina Wild, Christian Guelly,Thomas Bauernhofer,Hellmut Samonigg,Gerald Hoefler, and Nadia Dandachi:Evaluation of High-Resolution Melting Analysis as a Diagnostic Tool to Detect the BRAF V600E Mutation in Colorectal Tumors. Journal of Molecular Diagnostics 2009, 11,. 140-147.
37. Marie-Pierre Audrezet, Aure´ lia Dabricot,Ce´ dric Le Marechal,and Claude Ferec:Validation of High-Resolution DNA Melting Analysis for Mutation Scanning of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene. Journal of Molecular Diagnostics,2008, 10, 424-434.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42874-
dc.description.abstractWilm’s tumor 1, discovered to be important in kidney tumor of child, plays the role in regulating gene expression. For instance, WT1 in breast cancer acts as an oncogene, forming tumors or causing metastasis through activating c-myc, Bcl-2 and E-cadherin. On the other hand, WT1 in kidney tumor could inactivates c-myc, Bcl-2 and E-cadherin.Similar contradict results was found in patients with AML. CD34+ cell, from AML patients tended to have higher WT1 expression than those from normal patients. On the other hand, 15% of AML patients was with mutant WT1. Both of them demonstrated poor prognosis with standard chemotherapy. In clinical practice, WT1 could be as a biomarker for AML patients to monitor disease status.
The aim of this study is to develop an effective process to detect WT1 mutation, providing references for clinical diagnosis, follow-up management and prognostic evaluation. We coupled real-time PCR with the theorem of high resolution melting to set up a standard operation protocol(SOP) for differentiating mutant from normal WT1. In this protocol, LCGreen dye was used to intercalate double strand DNA and show fluorescence, but the fluorescence would disapper when double strand DNA dissociated into single strand DNA with increasing temperature. Comparing the difference of melting peaks by analytic software, we could differentiate the mutants from the wild types. Afterward, we confirmed the mutation type by direct sequencing or GeneScan. We believe this detecting process can decrease the cost effectively, and increase the sensitivity, compared to direct sequencing detecting method.
en
dc.description.provenanceMade available in DSpace on 2021-06-15T01:27:01Z (GMT). No. of bitstreams: 1
ntu-98-R96424022-1.pdf: 1040686 bytes, checksum: 7cadc8780b1ad268caf346ed424d38dc (MD5)
Previous issue date: 2009
en
dc.description.tableofcontents中文摘要…………………………………………………………………ii
英文摘要…………………………………………………………………iv
第一章引言………………………………………………………………1
第二章實驗目的…………………………………………………………5
第三章實驗材料及方法…………………………………………………6
第四章實驗結果…………………………………………………………13
第五章討論………………………………………………………………18
圖…………………………………………………………………………22
表…………………………………………………………………………37
參考文獻…………………………………………………………………47
附圖………………………………………………………………………52
附表………………………………………………………………………55
dc.language.isozh-TW
dc.title建立偵測急性骨髓白血病WT1基因突變的檢驗流程zh_TW
dc.titleDeveloping a sustainable process to screen and identify WT1 mutation in patients with AMLen
dc.typeThesis
dc.date.schoolyear97-2
dc.description.degree碩士
dc.contributor.oralexamcommittee顏瑞鴻,呂健惠,林淑萍
dc.subject.keyword高分辨熔解曲線,WT1,螢光染劑,急性骨髓性白血病,完全緩解,zh_TW
dc.subject.keywordHigh resolution melting(HRM),WT1,fluorescent dye,acute myloid leukemia(AML),complete remission,en
dc.relation.page55
dc.rights.note有償授權
dc.date.accepted2009-07-23
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept醫學檢驗暨生物技術學研究所zh_TW
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