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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊雅倩 | |
| dc.contributor.author | Wen-Chi Chen | en |
| dc.contributor.author | 陳紋綺 | zh_TW |
| dc.date.accessioned | 2021-06-13T01:21:07Z | - |
| dc.date.available | 2021-12-31 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-03 | |
| dc.identifier.citation | 1. Soreide K, Janssen EA, Soiland H et al. Microsatellite instability in colorectal cancer. Br J Surg 2006; 93: 395-406.
2. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-767. 3. Jass JR, Young J, Leggett BA. Evolution of colorectal cancer: change of pace and change of direction. J Gastroenterol Hepatol 2002; 17: 17-26. 4. Jass JR, Whitehall VL, Young J, Leggett BA. Emerging concepts in colorectal neoplasia. Gastroenterology 2002; 123: 862-876. 5. Haydon AM, Jass JR. Emerging pathways in colorectal-cancer development. Lancet Oncol 2002; 3: 83-88. 6. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996; 87: 159-170. 7. Postma C, Hermsen MA, Coffa J et al. Chromosomal instability in flat adenomas and carcinomas of the colon. J Pathol 2005; 205: 514-521. 8. Hermsen M, Postma C, Baak J et al. Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology 2002; 123: 1109-1119. 9. Choi SW, Lee KJ, Bae YA et al. Genetic classification of colorectal cancer based on chromosomal loss and microsatellite instability predicts survival. Clin Cancer Res 2002; 8: 2311-2322. 10. Meijer GA, Hermsen MA, Baak JP et al. Progression from colorectal adenoma to carcinoma is associated with non-random chromosomal gains as detected by comparative genomic hybridisation. J Clin Pathol 1998; 51: 901-909. 11. Kennedy MV, Zarling EJ. Answers to 10 key questions on diverticular disease of the colon. Compr Ther 1998; 24: 364-369. 12. Liu B, Farrington SM, Petersen GM et al. Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med 1995; 1: 348-352. 13. Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 2008; 135: 1079-1099. 14. Nakagawa H, Lockman JC, Frankel WL et al. Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res 2004; 64: 4721-4727. 15. Chung DC, Rustgi AK. The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med 2003; 138: 560-570. 16. Kolodner RD, Tytell JD, Schmeits JL et al. Germ-line msh6 mutations in colorectal cancer families. Cancer Res 1999; 59: 5068-5074. 17. Beck NE, Tomlinson IP, Homfray T et al. Genetic testing is important in families with a history suggestive of hereditary non-polyposis colorectal cancer even if the Amsterdam criteria are not fulfilled. Br J Surg 1997; 84: 233-237. 18. Walther A, Johnstone E, Swanton C et al. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 2009; 9: 489-499. 19. Goel A, Nagasaka T, Arnold CN et al. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology 2007; 132: 127-138. 20. Kambara T, Simms LA, Whitehall VL et al. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 2004; 53: 1137-1144. 21. Weisenberger DJ, Siegmund KD, Campan M et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006; 38: 787-793. 22. Shen L, Toyota M, Kondo Y et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci U S A 2007; 104: 18654-18659. 23. Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007; 50: 113-130. 24. Ogino S, Nosho K, Kirkner GJ et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 2009; 58: 90-96. 25. Samowitz WS, Sweeney C, Herrick J et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 2005; 65: 6063-6069. 26. Spring KJ, Zhao ZZ, Karamatic R et al. High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology 2006; 131: 1400-1407. 27. Kim MS, Lee J, Sidransky D. DNA methylation markers in colorectal cancer. Cancer Metastasis Rev 2010; 29: 181-206. 28. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol 2010; 28: 1057-1068. 29. Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358: 1148-1159. 30. Toyota M, Ahuja N, Ohe-Toyota M et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 1999; 96: 8681-8686. 31. Issa JP, Ottaviano YL, Celano P et al. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 1994; 7: 536-540. 32. Issa JP, Baylin SB, Belinsky SA. Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure. Cancer Res 1996; 56: 3655-3658. 33. Worthley DL, Whitehall VL, Buttenshaw RL et al. DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer. Oncogene 2010; 29: 1653-1662. 34. Hibi K, Sakata M, Kitamura YH et al. Demethylation of the CD133 gene is frequently detected in advanced colorectal cancer. Anticancer Res 2009; 29: 2235-2237. 35. Dukes C. The classification of cancer of the rectum. J. Pathol. Bacteriol. 1932; 35: 323. 36. Irizarry RA, Ladd-Acosta C, Wen B et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009; 41: 178-186. 37. Doi A, Park IH, Wen B et al. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet 2009; 41: 1350-1353. 38. Penn NW, Suwalski R, O'Riley C et al. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J 1972; 126: 781-790. 39. Globisch D, Munzel M, Muller M et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One 2010; 5: e15367. 40. Ito S, D'Alessio AC, Taranova OV et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010; 466: 1129-1133. 41. Zhang H, Zhang X, Clark E et al. TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine. Cell Res 2010; 20: 1390-1393. 42. Valinluck V, Sowers LC. Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res 2007; 67: 946-950. 43. Jin SG, Kadam S, Pfeifer GP. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res 2010; 38: e125. 44. Cannon SV, Cummings A, Teebor GW. 5-Hydroxymethylcytosine DNA glycosylase activity in mammalian tissue. Biochem Biophys Res Commun 1988; 151: 1173-1179. 45. Teitell M, Richardson B. DNA methylation in the immune system. Clin Immunol 2003; 109: 2-5. 46. Jiang Y, Langley B, Lubin FD et al. Epigenetics in the nervous system. J Neurosci 2008; 28: 11753-11759. 47. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128: 683-692. 48. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 2007; 8: 286-298. 49. Chuang LS, Ian HI, Koh TW et al. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 1997; 277: 1996-2000. 50. Bostick M, Kim JK, Esteve PO et al. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 2007; 317: 1760-1764. 51. Bourc'his D, Xu GL, Lin CS et al. Dnmt3L and the establishment of maternal genomic imprints. Science 2001; 294: 2536-2539. 52. Wade PA. Methyl CpG binding proteins: coupling chromatin architecture to gene regulation. Oncogene 2001; 20: 3166-3173. 53. Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 2006; 5: 37-50. 54. Zhou L, Cheng X, Connolly BA et al. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol 2002; 321: 591-599. 55. Ruter B, Wijermans PW, Lubbert M. Superiority of prolonged low-dose azanucleoside administration? Results of 5-aza-2'-deoxycytidine retreatment in high-risk myelodysplasia patients. Cancer 2006; 106: 1744-1750. 56. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007; 26: 5541-5552. 57. Stadler WM, Margolin K, Ferber S et al. A phase II study of depsipeptide in refractory metastatic renal cell cancer. Clin Genitourin Cancer 2006; 5: 57-60. 58. Marks PA, Dokmanovic M. Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert Opin Investig Drugs 2005; 14: 1497-1511. 59. Bhalla KN. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J Clin Oncol 2005; 23: 3971-3993. 60. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006; 5: 769-784. 61. Costello JF, Fruhwald MC, Smiraglia DJ et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 2000; 24: 132-138. 62. Toyota M, Ho C, Ahuja N et al. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 1999; 59: 2307-2312. 63. Huang TH, Perry MR, Laux DE. Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet 1999; 8: 459-470. 64. Gonzalgo ML, Liang G, Spruck CH, 3rd et al. Identification and characterization of differentially methylated regions of genomic DNA by methylation-sensitive arbitrarily primed PCR. Cancer Res 1997; 57: 594-599. 65. Laird PW. Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet 2010; 11: 191-203. 66. Siegmund KD, Laird PW. Analysis of complex methylation data. Methods 2002; 27: 170-178. 67. Thisse B, Thisse C. Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol 2005; 287: 390-402. 68. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004; 20: 781-810. 69. Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev 2005; 16: 233-247. 70. Tsang M, Dawid IB. Promotion and attenuation of FGF signaling through the Ras-MAPK pathway. Sci STKE 2004; 2004: pe17. 71. Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003; 116: 2627-2634. 72. Yamamoto A, Nagano T, Takehara S et al. Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF. Cell 2005; 120: 223-235. 73. Silva AC, Filipe M, Vitorino M et al. Developmental expression of Shisa-2 in Xenopus laevis. Int J Dev Biol 2006; 50: 575-579. 74. Nagano T, Takehara S, Takahashi M et al. Shisa2 promotes the maturation of somitic precursors and transition to the segmental fate in Xenopus embryos. Development 2006; 133: 4643-4654. 75. Hedge TA, Mason I. Expression of Shisa2, a modulator of both Wnt and Fgf signaling, in the chick embryo. Int J Dev Biol 2008; 52: 81-85. 76. Furushima K, Yamamoto A, Nagano T et al. Mouse homologues of Shisa antagonistic to Wnt and Fgf signalings. Dev Biol 2007; 306: 480-492. 77. Bourdon JC, Renzing J, Robertson PL et al. Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane. J Cell Biol 2002; 158: 235-246. 78. Zhu Y TA, Yamamoto A, Furukawa K, Tajima O, Tokuda N, et al. Expression and roles of a xenopus head-forming gene homologue in human cancer cell lines. Nagoya J Med Sci 2008; 70. 79. Trinh BN, Long TI, Laird PW. DNA methylation analysis by MethyLight technology. Methods 2001; 25: 456-462. 80. Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol 2010; 28: 1069-1078. 81. Ahn JB, Chung WB, Maeda O et al. DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer 2011; 117: 1847-1854. 82. Zhang Y, Rohde C, Tierling S et al. DNA methylation analysis by bisulfite conversion, cloning, and sequencing of individual clones. Methods Mol Biol 2009; 507: 177-187. 83. Campan M, Weisenberger DJ, Trinh B, Laird PW. MethyLight. Methods Mol Biol 2009; 507: 325-337. 84. Colella S, Shen L, Baggerly KA et al. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques 2003; 35: 146-150. 85. Royo JL, Hidalgo M, Ruiz A. Pyrosequencing protocol using a universal biotinylated primer for mutation detection and SNP genotyping. Nat Protoc 2007; 2: 1734-1739. 86. Weisenberger DJ, Trinh BN, Campan M et al. DNA methylation analysis by digital bisulfite genomic sequencing and digital MethyLight. Nucleic Acids Res 2008; 36: 4689-4698. 87. Vinci S, Giannarini G, Selli C et al. Quantitative methylation analysis of BCL2, hTERT, and DAPK promoters in urine sediment for the detection of non-muscle-invasive urothelial carcinoma of the bladder: A prospective, two-center validation study. Urol Oncol 2011; 29: 150-156. 88. Tost J, Gut IG. Analysis of gene-specific DNA methylation patterns by pyrosequencing technology. Methods Mol Biol 2007; 373: 89-102. 89. Mouro I, Halleck MS, Schlegel RA et al. Cloning, expression, and chromosomal mapping of a human ATPase II gene, member of the third subfamily of P-type ATPases and orthologous to the presumed bovine and murine aminophospholipid translocase. Biochem Biophys Res Commun 1999; 257: 333-339. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29840 | - |
| dc.description.abstract | 大腸直腸癌 (Colorectal cancer，CRC)自正常大腸黏膜細胞轉變成癌細胞乃是經由長時間累積基因變異所造成。而大腸直腸癌致癌機轉分成基因遺傳 (Genetic)及表觀基因 (Epigenetic)調控之路徑。本論文研究的Shisa3基因位於人類第四號染色體4p13，相較於鄰近正常黏膜組織，CRC腫瘤組織Shisa3基因mRNA的表現明顯下降，推測Shisa對於CRC可能具有相關的抑癌功能。至今，人類Shisa3基因之功能及其在癌症發展中所扮演的角色尚不清楚，因此，本論文主要研究目的是探討Shisa3基因表現於CRC中受抑制的機制及其臨床的相關性。首先，為確認Shisa3基因的表現量，我們利用RT-PCR及qRT-PCR檢測其在不同CRC細胞株及臨床檢體的mRNA表現，結果顯示：大部分癌細胞株及臨床腫瘤檢體中，Shisa3基因都表現下降。接著探討Shisa3基因的靜默機制 (silencing)，利用DNA套數分析及對偶基因失異合性的初步研究，結果顯示基因刪除不是抑制Shisa3基因表現的主要機制。於表觀基因調控之研究，我們利用DNA去甲基化藥物5-Aza-2’-deoxycytidine (5-aza-CdR)處理六株大腸直腸癌細胞株，發現五株細胞(83.3%)可明顯恢復Shisa3基因表現。同時，Shisa3基因自Promoter區域至Exon1間具有高密度的CpG位點分布，因此，我們利用亞硫酸鹽定序聚合酶連鎖反應 (bisulfate-sequencing PCR，BSP)檢測CRC細胞株及臨床檢體於Shisa3基因CpG高分布區內甲基化的情形，並找出最有可能調控此基因表現的CpG區域。接著針對特定CpG位點設計MethyLight和Pyrosequencing兩種方法確認Shisa3基因的CpG調控區並定量DNA甲基化程度。結果顯示：於CRC腫瘤之DNA甲基化程度明顯高於鄰近正常黏膜組織，同時DNA甲基化程度與Shisa3基因表現量具有負相關 (R2=0.3248, p<0.0001)。進行臨床相關性分析，發現：Shisa3基因發生高度甲基化與CRC疾病復發有顯著相關，同時病人之總存活率 (Overall survival, OS)和無疾病存活率 (Disease-free survival, DFS)亦明顯降低。因此， Shisa3基因高度甲基化可能做為CRC病患之疾病復發及存活率的預後分子標記。 | zh_TW |
| dc.description.abstract | Most colorectal cancer (CRC) results from a consequence of the accumulation of genetic alterations that transform normal colonic mucosa into adenocarcinoma. Previous reports indicated that pathogenesis of CRC involves two different mechanisms, namely genetic and epigenetic pathways. Shisa3 gene, which we focused on, locates on human chromosome 4p13. Compared with matched normal colon mucosa, the mRNA expression of Shisa3 gene was decreased in most CRC primary tumors. Accordingly, we propose that Shisa3 might have tumor suppressor function in CRC. Nowadays the role of Shisa3 in tumorigenesis is still unknown. Therefore, the aim of this study is to investigate Shisa3 gene silencing and it’s clinical correlation in CRC. First, we used CRC cell lines and primary tissues to determine mRNA expression of Shisa3 gene by RT-PCR and qRT-PCR. The results showed that down-regulation of Shisa3 in most CRC cell lines and primary tumors. To ascertain whether Shisa3 gene is silenced via genetic alterations in CRC, we performed Shisa3 DNA copy number and loss of heterozygosity (LOH) analyse. Our data showed that genetic deletion isn’t the major mechanism of Shisa3 gene silencing. Meanwhile, we found that Shisa3 expression in 5 of 6 (83.3%) CRC cell was restored after treatment with 5-aza-2’-deoxycytidine (5-Aza-CdR). Besides, high density CpG islands span from promoter to Exon 1 of Shisa3 gene. Accordingly, we analyzed DNA methylation status of Shisa3 at various CpG sites in CRC cell lines and primary CRC tissues by bisulfite-sequencing PCR (BSP). To investigate the possible regulation sites of DNA methylation in Shisa3, the DNA methylation level of Shisa3 was determined by MethyLight and pyrosequencing methods. The reverse correlation was observed between DNA methylation and mRNA expression of Shisa3 gene in CRC tumors (R2=0.3248, p<0.0001). Moreover, we revealed the impact of Shisa3 DNA methylation on patients’ overall survival and disease-free survival. In conclusion, the methylation level of Shisa3 gene might be a possible prognostic biomarker of CRC in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T01:21:07Z (GMT). No. of bitstreams: 1 ntu-100-R98424013-1.pdf: 5939626 bytes, checksum: 599772073c562d9c47489774415d58eb (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii 英文摘要 iv 縮寫表 vi 目次 vii 圖次 x 表次 xii 第一章 緒論 1 第一節 研究背景 1 1. 概論大腸直腸癌 1 2. 大腸直腸癌之致癌機轉 1 3. 大腸直腸癌之分期 4 第二節 表觀基因修飾作用 4 1. 表觀基因修飾調控 4 2. 表觀基因修飾藥物 7 3. 基因DNA甲基化之分析技術 7 第三節 Shisa homolog 3 (Xenopus laevis)之相關研究 8 第四節 研究動機及目的 9 第二章 材料與方法 11 第一節 實驗材料 11 1. 細胞株 11 2. 大腸直腸癌組織檢體 11 3. 正常人之周邊血液 11 第二節 實驗方法 12 1. 抽取核酸 12 2. Shisa3反轉錄聚合酶連鎖反應 14 3. Shisa3即時定量反轉錄聚合酶連鎖反應 15 4. Shisa3 DNA套數檢測分析 (copy number assay) 15 5. 甲基化基因分析技術 16 6. DNA去甲基化藥物5-Aza-2’-deoxycytidine處理大腸直腸癌細株 18 7. 對偶基因失異合性 (Loss of heterozygosity，LOH)研究 18 8. MethyLight assay甲基化分析 19 9. Pyrosequencing 甲基化分析 20 10. 統計分析 21 第三章 研究結果 23 第一節 大腸直腸癌腫瘤Shisa3基因mRNA表現明顯降低 23 第二節 大腸直腸癌細胞株之Shisa3基因表現 23 第三節Shisa3 基因之DNA套數分析 24 第四節 Shisa3基因之對偶基因失異合性研究 24 1. 微衛星標記之選定 24 2. ATP8A1 基因於大腸直腸腫瘤之mRNA表現無明顯變化 25 第五節 DNA去甲基化藥物5-Aza-2’-deoxycytidine處理可恢復大腸直腸癌細胞之Shisa3基因表現 25 第六節Shisa3基因甲基化調控區域的鑑定與定量分析 26 1. BSP方法鑑定Shisa3基因甲基化調控區域 26 2. BSP2區域之DNA甲基化定量分析 28 第七節 Shisa3基因高度甲基化於大腸直腸癌之臨床相關性 29 第四章 討論 31 圖 38 表 56 參考文獻 68 附錄圖 77 附錄表 85 | |
| dc.language.iso | zh-TW | |
| dc.subject | Pyrosequencing | zh_TW |
| dc.subject | 大腸直腸癌 | zh_TW |
| dc.subject | Shisa3 | zh_TW |
| dc.subject | DNA甲基化 | zh_TW |
| dc.subject | MethyLight | zh_TW |
| dc.subject | Shisa3 | en |
| dc.subject | Pyrosequencing | en |
| dc.subject | MethyLight | en |
| dc.subject | DNA methylation | en |
| dc.subject | Colorectal cancer | en |
| dc.title | 探討Shisa3基因於大腸直腸癌之基因靜默機制
及其臨床相關性 | zh_TW |
| dc.title | Study of Shisa3 gene silencing and it’s clinical correlation in colorectal cancer | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林亮音,俞松良,蔡明宏 | |
| dc.subject.keyword | 大腸直腸癌,Shisa3,DNA甲基化,MethyLight,Pyrosequencing, | zh_TW |
| dc.subject.keyword | Colorectal cancer,Shisa3,DNA methylation,MethyLight,Pyrosequencing, | en |
| dc.relation.page | 92 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-03 | |
| 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 |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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