References133. L<strong>in</strong>d GE, Thorstensen L, Løvig T, Mel<strong>in</strong>g GI, Hamel<strong>in</strong> R, Rognum TO, Esteller M,Lothe RA (2004) A CpG isl<strong>and</strong> hypermethylation profile of primary colorectalcarc<strong>in</strong>omas <strong>and</strong> colon cancer cell l<strong>in</strong>es. Mol Cancer 3:28134. De Luca A, Bucc<strong>in</strong>o A, Gianni D, Mang<strong>in</strong>o M, Giust<strong>in</strong>i S, Richetta A, Divona L,Calvieri S, M<strong>in</strong>garelli R, Dallapiccola B (2003) NF1 gene analysis based onDHPLC. Hum Mutat 21(2): 171-172135. Upadhyaya M, Kluwe L, Spurlock G, Monem B, Majounie E, Mantripragada K,Ruggieri M, Chuzha<strong>no</strong>va N, Evans DG, Ferner R, Thomas N, Guha A, Mautner V(2007) Germl<strong>in</strong>e <strong>and</strong> somatic NF1 gene mutation spectrum <strong>in</strong> NF1-associatedmalignant peripheral nerve sheath tumors (MPNSTs). Hum Mutat 29(1): 74-82136. Bottillo I, Ahlquist T, Brekke HR, Danielsen SA, van den Berg E, Mertens F, LotheRA, Dallapiccola B. Germl<strong>in</strong>e <strong>and</strong> somatic NF1 mutations <strong>in</strong> sporadic <strong>and</strong>NF1-associated malignant peripheral nerve sheath tumors. The Journal ofPathology. In Press137. Shapiro R, Weisgras JM (1970) Bisulfite-catalyzed transam<strong>in</strong>ation of cytos<strong>in</strong>e<strong>and</strong> cytid<strong>in</strong>e. Biochem Biophys Res Commun 40(4): 839-843138. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL,Paul CL (1992) A ge<strong>no</strong>mic sequenc<strong>in</strong>g protocol that yields a positive display of5-methylcytos<strong>in</strong>e residues <strong>in</strong> <strong>in</strong>dividual DNA str<strong>and</strong>s. Proc Natl Acad Sci U S A89(5): 1827-1831139. Clark SJ, Harrison J, Paul CL, Frommer M (1994) High sensitivity mapp<strong>in</strong>g ofmethylated cytos<strong>in</strong>es. Nucleic Acids Res 22(15): 2990-2997140. Clark SJ (2005) Study<strong>in</strong>g Mammalian DNA Methylation: Bisulfite Modification. In:Esteller M (ed) DNA Methylation - Approaches, Methods, <strong>and</strong> Applications.CRC press, pp 53-63141. Herman JG, Graff JR, Myöhänen S, Nelk<strong>in</strong> BD, Bayl<strong>in</strong> SB (1996) MethylationspecificPCR: a <strong>no</strong>vel PCR assay for methylation status of CpG isl<strong>and</strong>s. ProcNatl Acad Sci U S A 93(18): 9821-9826142. Jones PA (1999) The DNA methylation paradox. Trends Genet 15(1): 34-37143. Deng G, Chen A, Hong J, Chae HS, Kim YS (1999) Methylation of CpG <strong>in</strong> asmall region of the hMLH1 promoter <strong>in</strong>variably correlates with the absence ofgene expression. Cancer Res 59(9): 2029-2033144. Herman JG (2005) Bisulfite PCR-Based Techniques for the Study of DNAMethylation. In: Esteller M (ed) DNA Methylation - Approaches, Methods, <strong>and</strong>Applications. CRC press, pp 65-7278
References145. Oefner PJ, Underhill P (1995) Comparative DNA sequenc<strong>in</strong>g by denatur<strong>in</strong>ghigh-performance liquid chromatography (DHPLC). Am J Hum Genet57(A266):146. Xiao W, Oefner PJ (2001) Denatur<strong>in</strong>g high-performance liquidchromatography: A review. Hum Mutat 17(6): 439-474147. Jones AC, Aust<strong>in</strong> J, Hansen N, Hoogendoorn B, Oefner PJ, Cheadle JP, O'Do<strong>no</strong>vanMC (1999) Optimal temperature selection for mutation detection bydenatur<strong>in</strong>g HPLC <strong>and</strong> comparison to s<strong>in</strong>gle-str<strong>and</strong>ed conformationpolymorphism <strong>and</strong> heteroduplex analysis. Cl<strong>in</strong> Chem 45(8 Pt 1): 1133-1140148. Orita M, Suzuki Y, Sekiya T, Hayashi K (1989) Rapid <strong>and</strong> sensitive detection ofpo<strong>in</strong>t mutations <strong>and</strong> DNA polymorphisms us<strong>in</strong>g the polymerase cha<strong>in</strong>reaction. Ge<strong>no</strong>mics 5(4): 874-879149. Sørlie T, Johnsen H, Vu P, L<strong>in</strong>d GE, Lothe RA, Børresen-Dale AL (2005) Mutationscreen<strong>in</strong>g of the TP53 gene by temporal temperature gradient gelelectrophoresis. Methods Mol Biol 291 207-216150. Ganguly A, Rock MJ, Prockop DJ (1993) Conformation-sensitive gelelectrophoresis for rapid detection of s<strong>in</strong>gle-base differences <strong>in</strong> doublestr<strong>and</strong>edPCR products <strong>and</strong> DNA fragments: evidence for solvent-<strong>in</strong>ducedbends <strong>in</strong> DNA heteroduplexes. Proc Natl Acad Sci U S A 90(21): 10325-10329151. Fischer SG, Lerman LS (1983) DNA fragments differ<strong>in</strong>g by s<strong>in</strong>gle base-pairsubstitutions are separated <strong>in</strong> denatur<strong>in</strong>g gradient gels: correspondence withmelt<strong>in</strong>g theory. Proc Natl Acad Sci U S A 80(6): 1579-1583152. Stanssens P, Zabeau M, Meersseman G, Remes G, Gansemans Y, Storm N, HartmerR, Honisch C, Rodi CP, Bocker S, van den BD (2004) High-throughput MALDI-TOF discovery of ge<strong>no</strong>mic sequence polymorphisms. Ge<strong>no</strong>me Res 14(1): 126-133153. De Luca A, Schir<strong>in</strong>zi A, Bucc<strong>in</strong>o A, Bottillo I, S<strong>in</strong>ibaldi L, Torrente I, Ciavarella A,Dottor<strong>in</strong>i T, Porciello R, Giust<strong>in</strong>i S, Calvieri S, Dallapiccola B (2004) <strong>Novel</strong> <strong>and</strong>recurrent mutations <strong>in</strong> the NF1 gene <strong>in</strong> Italian patients withneurofibromatosis type 1. Hum Mutat 23(6): 629154. De Luca A, Bottillo I, Dasdia MC, Morella A, Lanari V, Bernard<strong>in</strong>i L, Divona L,Giust<strong>in</strong>i S, S<strong>in</strong>ibaldi L, <strong>Novel</strong>li A, Torrente I, Schir<strong>in</strong>zi A, Dallapiccola B (2007)Deletions of NF1 gene <strong>and</strong> exons detected by multiplex ligation-dependentprobe amplification. J Med Genet 44(12): 800-808155. Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, Uhlen M (1993)Analysis of heterogeneous viral populations by direct DNA sequenc<strong>in</strong>g.Biotechniques 15(1): 120-12779
- Page 1 and 2:
Novel genetic and epigenetic altera
- Page 3 and 4:
TABLE OF CONTENTSACKNOWLEDGEMENTS .
- Page 5 and 6:
ACKNOWLEDGEMENTSThe present work ha
- 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
- 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 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 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
- Page 94 and 95: Journal of Translational Medicine 2
- Page 96 and 97: Journal of Translational Medicine 2
- Page 98 and 99: Journal of Translational Medicine 2
- Page 100 and 101: Journal of Translational Medicine 2
- 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
- Page 110 and 111: ADAMTS1 CDKN2A CRABP1 HOXA9 MAL MGM
- 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
- Page 119 and 120: Volume 10 Number 7 July 2008 pp. 68
- Page 121 and 122: 682 RAS Signaling in Colorectal Car
- Page 123 and 124: 684 RAS Signaling in Colorectal Car
- Page 125 and 126: 686 RAS Signaling in Colorectal Car
- Page 127: Table W2. Detailed Somatic Events o
- Page 131 and 132:
Identification of RCC2 as a prognos
- Page 133 and 134:
INTRODUCTIONMicrosatellite instabil
- Page 135 and 136:
unselected series of primary tumors
- Page 137 and 138:
specificity, i.e. that they only am
- Page 139 and 140:
On the assumption that DNA repair a
- Page 141 and 142:
In order to ensure that gene mutati
- Page 143 and 144:
Figure 2. Mutation frequency differ
- Page 145 and 146:
and TAF1B (0.50), ACVR2A and ASTE1
- Page 147 and 148:
Multivariate analysesA multivariate
- Page 149 and 150:
When comparing our findings of muta
- Page 151 and 152:
The test series included a low numb
- Page 153 and 154:
entering M-phase remains to be seen
- Page 155 and 156:
12. Duval A, Reperant M, Hamelin R
- Page 157 and 158:
34. Martineau-Thuillier S, Andreass
- Page 159:
AppendicesAppendix I:List of abbrev
- Page 163 and 164:
Critical Reviews TM in Oncogenesis,
- Page 165 and 166:
TARGET GENES OF MSI COLORECTAL CANC
- Page 167 and 168:
TARGET GENES OF MSI COLORECTAL CANC
- Page 169 and 170:
TARGET GENES OF MSI COLORECTAL CANC
- Page 171 and 172:
TARGET GENES OF MSI COLORECTAL CANC
- Page 173 and 174:
TARGET GENES OF MSI COLORECTAL CANC
- Page 175 and 176:
TARGET GENES OF MSI COLORECTAL CANC
- Page 177 and 178:
TARGET GENES OF MSI COLORECTAL CANC
- Page 179 and 180:
TARGET GENES OF MSI COLORECTAL CANC
- Page 181 and 182:
TARGET GENES OF MSI COLORECTAL CANC
- Page 183 and 184:
TARGET GENES OF MSI COLORECTAL CANC
- Page 185 and 186:
TARGET GENES OF MSI COLORECTAL CANC
- Page 187 and 188:
TARGET GENES OF MSI COLORECTAL CANC
- Page 189 and 190:
TARGET GENES OF MSI COLORECTAL CANC
- Page 191:
TARGET GENES OF MSI COLORECTAL CANC