Novel genetic and epigenetic alterations in ... - Ous-research.no

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IntroductionFUTURE PERSPECTIVES ............................................................................................................65REFERENCES..................................................................................................................................68ORIGINAL ARTICLES......................................................................................................................APPENDIX............................................................................................................................................Appendix I. Associated paper..........................................................................................................Appendix II. Abbreviations .............................................................................................................
ACKNOWLEDGEMENTSThe present work has been performed at the Department of Cancer Prevention, Institute forCancer Research at Rikshospitalet University Hospital – Radiumhospitalet and wassupported by the Research Council of Norway and Centre for Cancer Biomedicine.I am grateful for working under my supervisor, Professor Ragnhild Lothe, who with hersupreme knowledge, enthusiasm and kindness has made it easy to thrive both scientificallyand socially. Especially big thanks to post doc Guro Lind for being invaluable, both byhelping out in the lab as well as with preparing manuscripts.A big “grazie” to Professor Bruno Dallapiccola for inviting me to his excellent researchfacilities in Rome to work, and also to Irene Bottillo who with her excellent laboratory skillsand including, friendly nature made my stay scientifically as well as socially very rewarding.A big thanks goes to co-authors and collaborators for very good biological material, clinicaldata and scientific input. I would also like to acknowledge Professor Arild Nesbakken forbeing my official link to the Faculty of Medicine, as well as contributing with valuablefeedback on the clinical aspects of the thesis.Kudos to all my good friends and colleagues in the department who have meant the world tome. Special thanks to Helge and Marianne for making my day as we’ve been my office matesfor 5 years. An important factor in completing this thesis is the personnel the Narvesenkiosk who ensured that my blood-sugar was at a constantly elevated level. Jan-Ivar Hansen,my biology teacher at Bjørknes Privatskole was so in love with biology that it was impossiblenot to be the same. Thanks!This thesis had never even been started if it wasn’t for my wonderful wife, Hege and myparents. Her for making me not want to study medicine in Hungary, and them for teachingme to have high standards and big aims. I love you!Oslo, December 23 rd 2008
Page 1 and 2: Novel genetic and epigenetic altera
Page 3: TABLE OF CONTENTSACKNOWLEDGEMENTS .
Page 7 and 8: Prefacetechnology[3]. This new tech
Page 10 and 11: SummaryThe subgroup of carcinomas w
Page 12 and 13: Introduction“Epigenetic inheritan
Page 14 and 15: Introductionamino acid change it is
Page 16 and 17: Introductionmethylation during embr
Page 18 and 19: IntroductionDNA is most of the time
Page 20 and 21: IntroductionFigure 5. DNA methylati
Page 22 and 23: 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
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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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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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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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