RØYRVIK ET AL.<strong>in</strong>stability high (MSI-H) colon cancers correlates with cl<strong>in</strong>ico-pathological parameters:A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR <strong>and</strong>BLM genes. Int J Cancer. 2000;89:230–5.91. Catasus L, Matias-Guiu X, Mach<strong>in</strong> P, Zan<strong>no</strong>ni GF, Scambia G, edetti-PaniciP, Prat J. Frameshift mutations at cod<strong>in</strong>g mo<strong>no</strong>nucleotide repeat microsatellites<strong>in</strong> endometrial carc<strong>in</strong>oma with microsatellite <strong>in</strong>stability. Cancer. 2000;88:2290–7.92. Johannsdottir JT, Jonasson JG, Bergthorsson JT, Amundadottir LT, MagnussonJ, Egilsson V, Ingvarsson S. The effect of mismatch repair deficiency on tumourigenesis;microsatellite <strong>in</strong>stability affect<strong>in</strong>g genes conta<strong>in</strong><strong>in</strong>g short repeatedsequences. Int J Oncol. 2000;16:133–9.93. Percesepe A, Pedroni M, Sala E, Menigatti M, Borghi F, Losi L, Viel A, GenuardiM, Benatti P, Roncucci L, Peltomaki P, Ponz de LM. Ge<strong>no</strong>mic <strong>in</strong>stability<strong>and</strong> target gene mutations <strong>in</strong> colon cancers with different degrees of allelicshifts. Genes Chromosomes Cancer. 2000;27:424–9.94. Semba S, Ouyang H, Han SY, Kato Y, Horii A. Analysis of the c<strong>and</strong>idate targetgenes for mutation <strong>in</strong> microsatellite <strong>in</strong>stability-positive cancers of the colorectum,stomach, <strong>and</strong> endometrium. Int J Oncol. 2000;16:731–7.95. Simms LA, Young J, Wick<strong>in</strong>g C, Meltzer SJ, Jass JR, Leggett BA. The apoptoticregulatory gene, BCL10, is mutated <strong>in</strong> sporadic mismatch repair deficientcolorectal cancers. Cell Death Differ. 2000;7:236–7.96. Cal<strong>in</strong> G, Ranzani GN, Amadori D, Herlea V, Matei I, Barbanti-Broda<strong>no</strong> G,Negr<strong>in</strong>i M. Somatic frameshift mutations <strong>in</strong> the Bloom syndrome BLM geneare frequent <strong>in</strong> sporadic gastric carc<strong>in</strong>omas with microsatellite mutator phe<strong>no</strong>type.BMC Genet. 2001;2:14. Epub. 2001 Aug 14.14.97. Gras E, Catasus L, Arguelles R, More<strong>no</strong>-Bue<strong>no</strong> G, Palacios J, Gamallo C, Matias-GuiuX, Prat J. Microsatellite <strong>in</strong>stability, MLH-1 promoter hypermethylation,<strong>and</strong> frameshift mutations at cod<strong>in</strong>g mo<strong>no</strong>nucleotide repeat microsatellites<strong>in</strong> ovarian tumors. Cancer. 2001;92:2829–36.98. Lee HS, Lee BL, Kim SH, Woo DK, Kim HS, Kim WH. Microsatellite <strong>in</strong>stability<strong>in</strong> synchro<strong>no</strong>us gastric carc<strong>in</strong>omas. Int J Cancer. 2001;91:619–24.99. Miyaki M, Iijima T, Shiba K, Aki T, Kita Y, Yasu<strong>no</strong> M, Mori T, Kuroki T,Iwama T. Alterations of repeated sequences <strong>in</strong> 5' upstream <strong>and</strong> cod<strong>in</strong>g regions<strong>in</strong> colorectal tumors from patients with hereditary <strong>no</strong>npolyposis colorectal cancer<strong>and</strong> Turcot syndrome. Oncogene. 2001;20:5215–8.100. Sh<strong>in</strong> KH, Park YJ, Park JG. PTEN gene mutations <strong>in</strong> colorectal cancers display<strong>in</strong>gmicrosatellite <strong>in</strong>stability. Cancer Lett. 2001;174:189–94.101. Togo G, Shiratori Y, Okamoto M, Yamaji Y, Matsumura M, Sa<strong>no</strong> T, MotojimaT, Omata M. Relationship between grade of microsatellite <strong>in</strong>stability <strong>and</strong> target250
TARGET GENES OF MSI COLORECTAL CANCERgenes of mismatch repair pathways <strong>in</strong> sporadic colorectal carc<strong>in</strong>oma. Dig DisSci. 2001;46:1615–22.102. Furlan D, Casati B, Cerutti R, Facco C, Terraccia<strong>no</strong> L, Capella C, ChiaravalliAM. Genetic progression <strong>in</strong> sporadic endometrial <strong>and</strong> gastro<strong>in</strong>test<strong>in</strong>al cancerswith high microsatellite <strong>in</strong>stability. J Pathol. 2002;197:603–9.103. Moriyama H, Sasamoto H, Kambara T, Matsubara N, Ikeda M, Baba S, MeltzerSJ, Lynch HT, Shimizu K, Tanaka N. E2F-4 mutation <strong>in</strong> hereditary <strong>no</strong>npolyposiscolorectal cancer. J Exp Cl<strong>in</strong> Cancer Res. 2002;21:185–9.104. Jeong SY, Sh<strong>in</strong> KH, Sh<strong>in</strong> JH, Ku JL, Sh<strong>in</strong> YK, Park SY, Kim WH, Park JG.Microsatellite <strong>in</strong>stability <strong>and</strong> mutations <strong>in</strong> DNA mismatch repair genes <strong>in</strong> sporadiccolorectal cancers. Dis Colon Rectum. 2003;46:1069–77.105. Potocnik U, Glavac D, Ravnik-Glavac M. Identification of <strong>no</strong>vel genes withsomatic frameshift mutations with<strong>in</strong> cod<strong>in</strong>g mo<strong>no</strong>nucleotide repeats <strong>in</strong> colorectaltumors with high microsatellite <strong>in</strong>stability. Genes Chromosomes Cancer.2003;36:48–56.106. Trojan J, Brieger A, Raedle J, Weber N, Kriener S, Kronenberger B, CasparyWF, Zeuzem S. BAX <strong>and</strong> caspase-5 frameshift mutations <strong>and</strong> spontaneousapoptosis <strong>in</strong> colorectal cancer with microsatellite <strong>in</strong>stability. Int J ColorectalDis. 2004;19:538–44.107. Vassileva V, Millar A, Briollais L, Chapman W, Bapat B. Apoptotic <strong>and</strong>growth regulatory genes as mutational targets <strong>in</strong> mismatch repair deficient endometrioidade<strong>no</strong>carc<strong>in</strong>omas of young patients. Oncol Rep. 2004;11:931–7.108. Fern<strong>and</strong>ez-Peralta AM, Nejda N, Oliart S, Med<strong>in</strong>a V, Azcoita MM, Gonzalez-Aguilera JJ. Significance of mutations <strong>in</strong> TGFBR2 <strong>and</strong> BAX <strong>in</strong> neoplastic progression<strong>and</strong> patient outcome <strong>in</strong> sporadic colorectal tumors with high-frequencymicrosatellite <strong>in</strong>stability. Cancer Genet Cytogenet. 2005;157:18–24.109. Chen GT, Zhu ZG, Y<strong>in</strong> HR, Liu BY, Ji J, Zhang J, L<strong>in</strong> YZ. [The relationshipbetween frameshift mutations of transform<strong>in</strong>g growth factor-beta type II receptor,<strong>in</strong>sul<strong>in</strong> growth factor II receptor, bcl-2 associated X prote<strong>in</strong>, E2F4 <strong>and</strong> microsatellite<strong>in</strong>stability <strong>in</strong> gastric carc<strong>in</strong>oma]. Zhonghua Wai Ke Za Zhi.2006;44:344–8.110. Cal<strong>in</strong> G, Herlea V, Barbanti-Broda<strong>no</strong> G, Negr<strong>in</strong>i M. The cod<strong>in</strong>g region of theBloom syndrome BLM gene <strong>and</strong> of the CBL proto-oncogene is mutated <strong>in</strong> <strong>genetic</strong>allyunstable sporadic gastro<strong>in</strong>test<strong>in</strong>al tumors. Cancer Res. 1998;58:3777–81.111. Chadwick RB, Jiang GL, Benn<strong>in</strong>gton GA, Yuan B, Johnson CK, Stevens MW,Niemann TH, Peltomaki P, Huang S, de la CA. C<strong>and</strong>idate tumor suppressorRIZ is frequently <strong>in</strong>volved <strong>in</strong> colorectal carc<strong>in</strong>ogenesis. Proc Natl Acad Sci U SA. 2000;97:2662–7.251
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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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IntroductionFigure 5. DNA methylati
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IntroductionFigure 6. Incidence rat
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IntroductionFigure 8. Tumor staging
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Introductioninasmuch as 80% of colo
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IntroductionInstabilities involved
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Introductionthere seems to be a fid
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Introductionsevere alterations are
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Introductionpopulation-wide screeni
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IntroductionFigure 12. Present and
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RESULTS IN BRIEFPaper Ia. “DNA hy
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Results in Briefinstability, and se
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Results in BriefUnivariate survival
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Discussionseveral factors, and full
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Discussionlow threshold, we increas
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DiscussionIt may seem like unnecess
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Discussionthan 96% DHPLC do not sta
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DiscussionFigure 13. Mutation detec
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DiscussionClinical impact of molecu
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Discussionmarkers with a very high
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Discussionchromosomes in metaphase[
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DiscussionThese examples underline
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Discussiongenes. One is based on mu
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CONCLUSIONSWe have identified novel
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Future PerspectivesMolecular risk a
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REFERENCES1. Breasted J (1930) The
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References29. Deng G, Chen A, Pong
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References57. Al-Sukhni W, Aronson
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References84. Kunkel TA (1993) Nucl
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ReferencesLeggett B, Levine J, Kim
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References133. Lind GE, Thorstensen
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References156. Meling GI, Lothe RA,
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ReferencesT, Song X, Day RH, Sledzi
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References196. Honda S, Haruta M, S
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ORIGINAL ARTICLESAPPENDIXAppendix I
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GASTROENTEROLOGY 2007;132:1631-1639
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Paper IbGuro E Lind, Terje Ahlquist
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Journal of Translational Medicine 2
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Journal of Translational Medicine 2
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Journal of Translational Medicine 2
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Journal of Translational Medicine 2
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Journal of Translational Medicine 2
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Paper IITerje Ahlquist, Guro E Lind
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BackgroundMost cases of colorectal
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ADAMTS1 CDKN2A CRABP1 HOXA9 MAL MGM
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pseudogene, leading to a high rate
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strands. Proc Natl Acad Sci U S A 1
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concomitant absence of transcript a
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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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