References29. Deng G, Chen A, Pong E, Kim YS (2001) Methylation <strong>in</strong> hMLH1 promoter<strong>in</strong>terferes with its b<strong>in</strong>d<strong>in</strong>g to transcription factor CBF <strong>and</strong> <strong>in</strong>hibits geneexpression. Oncogene 20(48): 7120-712730. Kondo Y, Issa JP (2004) Epi<strong>genetic</strong> changes <strong>in</strong> colorectal cancer. CancerMetastasis Rev 23(1-2): 29-3931. Lopez-Serra L, Esteller M (2008) Prote<strong>in</strong>s that b<strong>in</strong>d methylated DNA <strong>and</strong>human cancer: read<strong>in</strong>g the wrong words. Br J Cancer 98(12): 1881-188532. Lopez-Serra L, Ballestar E, Ropero S, Setien F, Billard LM, Fraga MF, Lopez-NievaP, Alam<strong>in</strong>os M, Guerrero D, Dante R, Esteller M (2008) Unmask<strong>in</strong>g ofepi<strong>genetic</strong>ally silenced c<strong>and</strong>idate tumor suppressor genes by removal ofmethyl-CpG-b<strong>in</strong>d<strong>in</strong>g doma<strong>in</strong> prote<strong>in</strong>s. Oncogene 27(25): 3556-356633. Miremadi A, Oestergaard MZ, Pharoah PD, Caldas C (2007) Cancer <strong>genetic</strong>s ofepi<strong>genetic</strong> genes. Hum Mol Genet 16 Spec No 1 R28-R4934. Ropero S, Fraga MF, Ballestar E, Hamel<strong>in</strong> R, Yamamoto H, Boix-Chornet M,Caballero R, Alam<strong>in</strong>os M, Setien F, Paz MF, Herranz M, Palacios J, Arango D,Orntoft TF, Aaltonen LA, Schwartz S Jr, Esteller M (2006) A truncat<strong>in</strong>g mutatio<strong>no</strong>f HDAC2 <strong>in</strong> human cancers confers resistance to histone deacetylase<strong>in</strong>hibition. Nat Genet 38(5): 566-56935. Jenuwe<strong>in</strong> T, Allis CD (2001) Translat<strong>in</strong>g the histone code. Science 293(5532):1074-108036. Felsenfeld G, Groud<strong>in</strong>e M (2003) Controll<strong>in</strong>g the double helix. Nature 421(6921):448-45337. Haig D, Westoby M (1989) Parent-specific gene expression <strong>and</strong> the triploidendosperm. Am Nat 134 147-15538. Burd M (2008) The Haig-Westoby model revisited. Am Nat 171(3): 400-40439. Eden S, Constancia M, Hashimshony T, Dean W, Goldste<strong>in</strong> B, Johnson AC, KeshetI, Reik W, Cedar H (2001) An upstream repressor element plays a role <strong>in</strong> Igf2impr<strong>in</strong>t<strong>in</strong>g. EMBO J 20(13): 3518-352540. Murrell A, Heeson S, Bowden L, Constancia M, Dean W, Kelsey G, Reik W (2001)An <strong>in</strong>tragenic methylated region <strong>in</strong> the impr<strong>in</strong>ted Igf2 gene augmentstranscription. EMBO Rep 2(12): 1101-110641. Esteller M, Herman JG (2002) Cancer as an epi<strong>genetic</strong> disease: DNAmethylation <strong>and</strong> chromat<strong>in</strong> <strong>alterations</strong> <strong>in</strong> human tumours. J Pathol 196(1): 1-742. Yoder JA, Walsh CP, Bestor TH (1997) Cytos<strong>in</strong>e methylation <strong>and</strong> the ecology of<strong>in</strong>trage<strong>no</strong>mic parasites. Trends Genet 13(8): 335-34070
References43. Fe<strong>in</strong>berg AP, Vogelste<strong>in</strong> B (1983) Hypomethylation dist<strong>in</strong>guishes genes of somehuman cancers from their <strong>no</strong>rmal counterparts. Nature 301(5895): 89-9244. Knudson AG, Jr. (1971) Mutation <strong>and</strong> cancer: statistical study ofret<strong>in</strong>oblastoma. Proc Natl Acad Sci U S A 68(4): 820-82345. Greger V, Passarge E, Hopp<strong>in</strong>g W, Messmer E, Horsthemke B (1989) Epi<strong>genetic</strong>changes may contribute to the formation <strong>and</strong> spontaneous regression ofret<strong>in</strong>oblastoma. Hum Genet 83(2): 155-15846. Sakai T, Toguchida J, Ohtani N, Y<strong>and</strong>ell DW, Rapaport JM, Dryja TP (1991) Allelespecifichypermethylation of the ret<strong>in</strong>oblastoma tumor-suppressor gene. Am JHum Genet 48(5): 880-88847. Deng S, Cal<strong>in</strong> GA, Croce CM, Coukos G, Zhang L (2008) Mechanisms ofmicroRNA deregulation <strong>in</strong> human cancer. Cell Cycle 7(17): 2643-264648. Guil S, Esteller M (2008) DNA methylomes, histone codes <strong>and</strong> miRNAs: Ty<strong>in</strong>git all together. Int J Biochem Cell Biol 41(1): 87-9549. Clark SJ (2007) Action at a distance: epi<strong>genetic</strong> silenc<strong>in</strong>g of large chromosomalregions <strong>in</strong> carc<strong>in</strong>ogenesis. Hum Mol Genet 16 Spec No 1 R88-R9550. Frigola J, Song J, Stirzaker C, H<strong>in</strong>shelwood RA, Pe<strong>in</strong>ado MA, Clark SJ (2006)Epi<strong>genetic</strong> remodel<strong>in</strong>g <strong>in</strong> colorectal cancer results <strong>in</strong> coord<strong>in</strong>ate genesuppression across an entire chromosome b<strong>and</strong>. Nat Genet 38(5): 540-54951. Novak P, Jensen T, Oshiro MM, Wozniak RJ, Nouzova M, Watts GS, Klimecki WT,Kim C, Futscher BW (2006) Epi<strong>genetic</strong> <strong>in</strong>activation of the HOXA gene cluster<strong>in</strong> breast cancer. Cancer Res 66(22): 10664-1067052. Park<strong>in</strong> DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CACancer J Cl<strong>in</strong> 55(2): 74-10853. Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW (2005) Colorectalcancer. Lancet 365(9454): 153-16554. Ahmed FE (2004) Effect of diet, life style, <strong>and</strong> otherenvironmental/chemopreventive factors on colorectal cancer development,<strong>and</strong> assessment of the risks. J Environ Sci Health C Environ Carc<strong>in</strong>og EcotoxicolRev 22(2): 91-14755. Bodmer WF (2006) Cancer <strong>genetic</strong>s: colorectal cancer as a model. J Hum Genet51(5): 391-39656. Lichtenste<strong>in</strong> P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M,Pukkala E, Skytthe A, Hemm<strong>in</strong>ki K (2000) Environmental <strong>and</strong> heritable factors<strong>in</strong> the causation of cancer--analyses of cohorts of tw<strong>in</strong>s from Sweden,Denmark, <strong>and</strong> F<strong>in</strong>l<strong>and</strong>. N Engl J Med 343(2): 78-8571
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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
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IntroductionDNA is most of the time
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- Page 24 and 25: IntroductionFigure 8. Tumor staging
- Page 26 and 27: Introductioninasmuch as 80% of colo
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- 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 72 and 73: References57. Al-Sukhni W, Aronson
- Page 74 and 75: References84. Kunkel TA (1993) Nucl
- Page 76 and 77: ReferencesLeggett B, Levine J, Kim
- 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
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- Page 98 and 99: Journal of Translational Medicine 2
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- Page 102 and 103: Journal of Translational Medicine 2
- Page 105: Paper IITerje Ahlquist, Guro E Lind
- Page 108 and 109: BackgroundMost cases of colorectal
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- 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
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682 RAS Signaling in Colorectal Car
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684 RAS Signaling in Colorectal Car
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686 RAS Signaling in Colorectal Car
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Table W2. Detailed Somatic Events o
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Identification of RCC2 as a prognos
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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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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC