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PREFACE“Is it just me? Or does everyonecome across genetics, genes, andDNA almost everywhere?”Madeleine AlbrightCancer as a disease has probably been around since the dawn of multicellular organisms. Theoldest written description of cancer is as early as the 17 th century BC in Egypt[1], but tracesof cancer has been detected as far back as in dinosaur fossils. According to the humoraltheory, it was believed that it was excess of black bile that was responsible for cancer as awhole. If this theory is correct the production of this body fluid must either have increasedrapidly over the last centuries, or increase with age, as one out of three people are diagnosedwith cancer today. Now we know that the black bile-theory did not stand the tooth of time,and that cancer is caused by both genes and environmental factors which via genetic andepigenetic abnormalities make normal regulation of e.g. cell cycle, apoptosis and signaling goawry.With improved life expectancy and a more sedentary lifestyle comes increased lifetime risk ofbeing diagnosed with cancer. Only in very rare occasions the primary tumor itself is fatal, butwhen the tumor metastasizes to distant and vital organs the mortality increases rapidly. As ittakes time from the first alterations via precursor lesions and the primary - to a fullymetastasized cancer, it leaves a window of opportunity in which the evolving cancer can bedetected and the person cured if the suitable tool or biomarkers is at hand.In September 2007, 4 years after the completion of the human genome project, the firstindividual genome was published[2]. Just a few moths later, the genome of James D. Watson,the co-discoverer of the double helix, was published using modern ultra high-throughput6
Prefacetechnology[3]. This new technology, which dramatically reduces cost and time consume,paves the way for individualized medicine and treatment. The price for sequencing anindividual genome is at the time being approximately $60.000. The ultimate goal is the $1000genome which will make it possible for the average Joe to be deciphered. By then it willsurely be easier to predict prognosis, treatment response and disease susceptibility amongpatients than what is the case today. Our job until then is to provide the community withgood and trustworthy data on which future diagnoses and treatments can be determined.7
Page 1 and 2: Novel genetic and epigenetic altera
Page 3 and 4: TABLE OF CONTENTSACKNOWLEDGEMENTS .
Page 5: ACKNOWLEDGEMENTSThe present work ha
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
Page 54 and 55: 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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