REFERENCES1. Breasted J (1930) The Edw<strong>in</strong> Smith Surgical Papyrus. University of ChicagoPress, Chicago,2. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J,Kirkness EF, Denisov G, L<strong>in</strong> Y, MacDonald JR, Pang AW, Shago M, Stockwell TB,Tsiamouri A, Bafna V, Bansal V, Kravitz SA, Busam DA, Beeson KY, McIntosh TC,Rem<strong>in</strong>gton KA, Abril JF, Gill J, Borman J, Rogers YH, Frazier ME, Scherer SW,Strausberg RL, Venter JC (2007) The diploid ge<strong>no</strong>me sequence of an <strong>in</strong>dividualhuman. PLoS Biol 5(10): e2543. Wheeler DA, Sr<strong>in</strong>ivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, ChenYJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP,Lupski JR, Ch<strong>in</strong>ault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Q<strong>in</strong> X, Muzny DM,Margulies M, We<strong>in</strong>stock GM, Gibbs RA, Rothberg JM (2008) The completege<strong>no</strong>me of an <strong>in</strong>dividual by massively parallel DNA sequenc<strong>in</strong>g. Nature452(7189): 872-8764. Mendel G (1866) Versuche über Plflanzen-hybriden. Verh<strong>and</strong>lungen desnaturforschenden Vere<strong>in</strong>es <strong>in</strong> Brünn. pp 3-475. Hershey AD, Chase M (1952) Independent functions of viral prote<strong>in</strong> <strong>and</strong> nucleicacid <strong>in</strong> growth of bacteriophage. J Gen Physiol 36(1): 39-566. Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure fordeoxyribose nucleic acid. Nature 171(4356): 737-7387. Suter CM, Mart<strong>in</strong> DI, Ward RL (2004) Germl<strong>in</strong>e epimutation of MLH1 <strong>in</strong><strong>in</strong>dividuals with multiple cancers. Nat Genet 36(5): 497-5018. Li E (2002) Chromat<strong>in</strong> modification <strong>and</strong> epi<strong>genetic</strong> reprogramm<strong>in</strong>g <strong>in</strong>mammalian development. Nat Rev Genet 3(9): 662-6739. Funk JO (1999) Cancer cell cycle control. Anticancer Res 19(6A): 4772-478010. Rajagopalan H, Nowak MA, Vogelste<strong>in</strong> B, Lengauer C (2003) The significance ofunstable chromosomes <strong>in</strong> colorectal cancer. Nat Rev Cancer 3(9): 695-70111. Nowell PC (1976) The clonal evolution of tumor cell populations. Science194(4260): 23-2812. Hanahan D, We<strong>in</strong>berg RA (2000) The hallmarks of cancer. Cell 100(1): 57-7013. Vogelste<strong>in</strong> B, K<strong>in</strong>zler KW (2004) Cancer genes <strong>and</strong> the pathways they control.Nat Med 10(8): 789-79968
References14. Grady WM, Carethers JM (2008) Ge<strong>no</strong>mic <strong>and</strong> Epi<strong>genetic</strong> Instability <strong>in</strong>Colorectal Cancer Pathogenesis. Gastroenterology 135(4): 1079-109915. Jones PA, Bayl<strong>in</strong> SB (2002) The fundamental role of epi<strong>genetic</strong> events <strong>in</strong> cancer.Nat Rev Genet 3(6): 415-42816. Fe<strong>in</strong>berg AP, Vogelste<strong>in</strong> B (1983) Hypomethylation of ras oncogenes <strong>in</strong> primaryhuman cancers. Biochem Biophys Res Commun 111(1): 47-5417. Esteller M (2008) Epi<strong>genetic</strong>s <strong>in</strong> cancer. N Engl J Med 358(11): 1148-115918. Dahl C, Ralfkiaer U, Guldberg P (2006) Methods for detection of subtlemutations <strong>in</strong> cancer ge<strong>no</strong>mes. Crit Rev Oncog 12(1-2): 41-7419. Hiller M, Platzer M (2008) Widespread <strong>and</strong> subtle: alternative splic<strong>in</strong>g at shortdistancet<strong>and</strong>em sites. Trends Genet 24(5): 246-25520. Darw<strong>in</strong> CR (1859) On the orig<strong>in</strong> of species by means of natural selection, or thepreservation of favoured races <strong>in</strong> the struggle for life.21. International Human Ge<strong>no</strong>me Sequenc<strong>in</strong>g Consortium (2004) F<strong>in</strong>ish<strong>in</strong>g theeuchromatic sequence of the human ge<strong>no</strong>me. Nature 431(7011): 931-94522. Futreal PA, Co<strong>in</strong> L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N,Stratton MR (2004) A census of human cancer genes. Nat Rev Cancer 4(3): 177-18323. Hotchkiss RD (1948) The quantitative separation of pur<strong>in</strong>es, pyrimid<strong>in</strong>es, <strong>and</strong>nucleosides by paper chromatography. J Biol Chem 175(1): 315-33224. Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of basesubstitution hotspots <strong>in</strong> Escherichia coli. Nature 274(5673): 775-78025. Shi H, Wang MX, Caldwell CW (2007) CpG isl<strong>and</strong>s: their potential asbiomarkers for cancer. Expert Rev Mol Diagn 7(5): 519-53126. Goll MG, Bestor TH (2005) Eukaryotic cytos<strong>in</strong>e methyltransferases. Annu RevBiochem 74:481-514. 481-51427. Chan TL, Yuen ST, Kong CK, Chan YW, Chan AS, Ng WF, Tsui WY, Lo MW,Tam WY, Li VS, Leung SY (2006) Heritable germl<strong>in</strong>e epimutation of MSH2 <strong>in</strong> afamily with hereditary <strong>no</strong>npolyposis colorectal cancer. Nat Genet 38(10): 1178-118328. Hitch<strong>in</strong>s MP, Wong JJ, Suthers G, Suter CM, Mart<strong>in</strong> DI, Hawk<strong>in</strong>s NJ, Ward RL(2007) Inheritance of a cancer-associated MLH1 germ-l<strong>in</strong>e epimutation. NEngl J Med 356(7): 697-70569
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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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- Page 26 and 27: Introductioninasmuch as 80% of colo
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- 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
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- Page 58 and 59: Discussionchromosomes in metaphase[
- Page 60 and 61: DiscussionThese examples underline
- Page 62 and 63: Discussiongenes. One is based on mu
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- Page 66 and 67: Future PerspectivesMolecular risk a
- 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 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
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- Page 91: Paper IbGuro E Lind, Terje Ahlquist
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- Page 108 and 109: BackgroundMost cases of colorectal
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- Page 112 and 113: pseudogene, leading to a high rate
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Volume 10 Number 7 July 2008 pp. 68
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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