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ReferencesLeggett B, Levine J, Kim M, French AJ, Thibodeau SN, Jass J, Haile R, Laird PW(2006) CpG island methylator phenotype underlies sporadic microsatelliteinstability and is tightly associated with BRAF mutation in colorectal cancer.Nat Genet 38(7): 787-793109. Lee S, Cho NY, Yoo EJ, Kim JH, Kang GH (2008) CpG island methylatorphenotype in colorectal cancers: comparison of the new and classic CpGisland methylator phenotype marker panels. Arch Pathol Lab Med 132(10):1657-1665110. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW,Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) ANational Cancer Institute Workshop on Microsatellite Instability for cancerdetection and familial predisposition: development of international criteria forthe determination of microsatellite instability in colorectal cancer. Cancer Res58(22): 5248-5257111. Ehrlich M (2003) The ICF syndrome, a DNA methyltransferase 3B deficiencyand immunodeficiency disease. Clin Immunol 109(1): 17-28112. Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathwaysin cancer. Oncogene 26(22): 3279-3290113. Oving IM, Clevers HC (2002) Molecular causes of colon cancer. Eur J Clin Invest32(6): 448-457114. Thorstensen L, Lothe RA (2003) The WNT Signaling Pathway and Its Role inHuman Solid Tumors. Atlas Genet Cytogenet Oncol Haematol.http://atlasgeneticsoncology.org/deep/WNTSignPathID20042.html115. Logan CY, Nusse R (2004) The Wnt signaling pathway in development anddisease. Annu Rev Cell Dev Biol 20:781-810. 781-810116. Fang JY, Richardson BC (2005) The MAPK signalling pathways and colorectalcancer. Lancet Oncol 6(5): 322-327117. Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7(8): 606-619118. Shaw RJ, Cantley LC (2006) Ras, PI(3)K and mTOR signalling controls tumourcell growth. Nature 441(7092): 424-430119. Massague J (2008) TGFbeta in Cancer. Cell 134(2): 215-230120. Xu Y, Pasche B (2007) TGF-beta signaling alterations and susceptibility tocolorectal cancer. Hum Mol Genet 16 Spec No 1 R14-R20121. Derynck R, Akhurst RJ (2007) Differentiation plasticity regulated by TGF-betafamily proteins in development and disease. Nat Cell Biol 9(9): 1000-100476
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Novel genetic and epigenetic altera
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TABLE OF CONTENTSACKNOWLEDGEMENTS .
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ACKNOWLEDGEMENTSThe present work ha
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Prefacetechnology[3]. This new tech
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SummaryThe subgroup of carcinomas w
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Introduction“Epigenetic inheritan
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Introductionamino acid change it is
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Introductionmethylation during embr
Page 18 and 19:
IntroductionDNA is most of the time
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IntroductionFigure 5. DNA methylati
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IntroductionFigure 6. Incidence rat
Page 24 and 25:
IntroductionFigure 8. Tumor staging
Page 26 and 27: Introductioninasmuch as 80% of colo
Page 28 and 29: IntroductionInstabilities involved
Page 30 and 31: Introductionthere seems to be a fid
Page 32 and 33: Introductionsevere alterations are
Page 34 and 35: Introductionpopulation-wide screeni
Page 36 and 37: IntroductionFigure 12. Present and
Page 38 and 39: RESULTS IN BRIEFPaper Ia. “DNA hy
Page 40 and 41: Results in Briefinstability, and se
Page 42 and 43: Results in BriefUnivariate survival
Page 44 and 45: Discussionseveral factors, and full
Page 46 and 47: Discussionlow threshold, we increas
Page 48 and 49: DiscussionIt may seem like unnecess
Page 50 and 51: Discussionthan 96% DHPLC do not sta
Page 52 and 53: DiscussionFigure 13. Mutation detec
Page 54 and 55: DiscussionClinical impact of molecu
Page 56 and 57: Discussionmarkers with a very high
Page 58 and 59: Discussionchromosomes in metaphase[
Page 60 and 61: DiscussionThese examples underline
Page 62 and 63: Discussiongenes. One is based on mu
Page 64 and 65: CONCLUSIONSWe have identified novel
Page 66 and 67: Future PerspectivesMolecular risk a
Page 68 and 69: REFERENCES1. Breasted J (1930) The
Page 70 and 71: References29. Deng G, Chen A, Pong
Page 72 and 73: References57. Al-Sukhni W, Aronson
Page 74 and 75: References84. Kunkel TA (1993) Nucl
Page 78 and 79: References133. Lind GE, Thorstensen
Page 80 and 81: References156. Meling GI, Lothe RA,
Page 82 and 83: ReferencesT, Song X, Day RH, Sledzi
Page 84 and 85: References196. Honda S, Haruta M, S
Page 86 and 87: ORIGINAL ARTICLESAPPENDIXAppendix I
Page 89 and 90: GASTROENTEROLOGY 2007;132:1631-1639
Page 91: Paper IbGuro E Lind, Terje Ahlquist
Page 94 and 95: Journal of Translational Medicine 2
Page 105: Paper IITerje Ahlquist, Guro E Lind
Page 108 and 109: BackgroundMost cases of colorectal
Page 110 and 111: ADAMTS1 CDKN2A CRABP1 HOXA9 MAL MGM
Page 112 and 113: pseudogene, leading to a high rate
Page 114 and 115: strands. Proc Natl Acad Sci U S A 1
Page 116 and 117: concomitant absence of transcript a
Page 119 and 120: Volume 10 Number 7 July 2008 pp. 68
Page 121 and 122: 682 RAS Signaling in Colorectal Car
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Table W2. Detailed Somatic Events o
Page 131 and 132:
Identification of RCC2 as a prognos
Page 133 and 134:
INTRODUCTIONMicrosatellite instabil
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unselected series of primary tumors
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specificity, i.e. that they only am
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On the assumption that DNA repair a
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In order to ensure that gene mutati
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Figure 2. Mutation frequency differ
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and TAF1B (0.50), ACVR2A and ASTE1
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Multivariate analysesA multivariate
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When comparing our findings of muta
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The test series included a low numb
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entering M-phase remains to be seen
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12. Duval A, Reperant M, Hamelin R
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34. Martineau-Thuillier S, Andreass
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AppendicesAppendix I:List of abbrev
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Critical Reviews TM in Oncogenesis,
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TARGET GENES OF MSI COLORECTAL CANC
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