Molecular Genetics of Familial Adenomatous Polyposis

  • Luis G. Carvajal-Carmona
  • Andrew Silver
  • Ian P. TomlinsonEmail author
Part of the M.D. Anderson Solid Tumor Oncology Series book series (MDA, volume 5)


With the advances in molecular genetics, the function of the APC gene has been and still is being described. In this chapter, a description of the APC protein, function, its relation to tumorigenesis, Familial Adenomatous Polyposis and other colorectal cancer syndromes will be discussed. Finally animal models which have been proven invaluable in the discovery of the APC protein function, will be described.


Molecular Genetics Familial Adenomatous Wnt signalling 


  1. 1.
    Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:59–170.CrossRefGoogle Scholar
  2. 2.
    Wheeler JM. Epigenetics, mismatch repair genes and colorectal cancer. Ann R Coll Surg Engl. 2005;87:15–20.PubMedCrossRefGoogle Scholar
  3. 3.
    Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:159–70.PubMedCrossRefGoogle Scholar
  4. 4.
    Luchtenborg M, Weijenberg MP, Roemen GM, de Bruine AP, van den Brandt PA, Lentjes MH, et al. APC mutations in sporadic colorectal carcinomas from the Netherlands Cohort Study. Carcinogenesis. 2004;25:1219–26.PubMedCrossRefGoogle Scholar
  5. 5.
    Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001;10:721–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Donis-Keller H, Green P, Helms C, Cartinhour S, Weiffenbach B, Stephens K, et al. A genetic linkage map of the human genome. Cell. 1987;51:319–37.PubMedCrossRefGoogle Scholar
  7. 7.
    Jeffreys AJ, Wilson V, Thein SL. Hypervariable ‘minisatellite’ regions in human DNA. Nature. 1985;314:67–73.PubMedCrossRefGoogle Scholar
  8. 8.
    Bodmer WF, Bailey CJ, Bodmer J, Bussey HJ, Ellis A, Gorman P, et al. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987;328:614–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Leppert M, Dobbs M, Scambler P, O’Connell P, Nakamura Y, Stauffer D, et al. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987;238:1411–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Solomon E, Voss R, Hall V, Bodmer WF, Jass JR, Jeffreys AJ, et al. Chromosome 5 allele loss in human colorectal carcinomas. Nature. 1987;328:616–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Herrera L, Kakati S, Gibas L, Pietrzak E, Sandberg AA. Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet. 1986;25:473–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Lynch HT, Smyrk T, McGinn T, Lanspa S, Cavalieri J, Lynch J, et al. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer. 1995;76:2427–33.PubMedCrossRefGoogle Scholar
  13. 13.
    Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992;256:668–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Lambertz S, Ballhausen WG. Identification of an alternative 5′ untranslated region of the adenomatous polyposis coli gene. Hum Genet. 1993;90:650–2.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheng H. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. IV. Paneth cells. Am J Anat. 1974;141:521–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Stappenbeck TS, Wong MH, Saam JR, Mysorekar IU, Gordon JI. Notes from some crypt watchers: regulation of renewal in the mouse intestinal epithelium. Curr Opin Cell Biol. 1998;10:702–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Senda T, Iizuka-Kogo A, Onouchi T, Shimomura A. Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. Med Mol Morphol. 2007;40:68–81.PubMedCrossRefGoogle Scholar
  18. 18.
    Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999;398:422–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Brocardo M, Nathke IS, Henderson BR. Redefining the subcellular location and transport of APC: new insights using a panel of antibodies. EMBO Rep. 2005;6:184–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Liu J, Xing Y, Hinds TR, Zheng J, Xu W. The third 20 amino acid repeat is the tightest binding site of APC for beta-catenin. J Mol Biol. 2006;360:133–44.PubMedCrossRefGoogle Scholar
  21. 21.
    Rubinfeld B, Albert I, Porfiri E, Munemitsu S, Polakis P. Loss of beta-catenin regulation by the APC tumor suppressor protein correlates with loss of structure due to common somatic mutations of the gene. Cancer Res. 1997;57:4624–30.PubMedGoogle Scholar
  22. 22.
    Bienz M. APC: the plot thickens. Curr Opin Genet Dev. 1999;9:595–603.PubMedCrossRefGoogle Scholar
  23. 23.
    Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, et al. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science. 1999;280:596–9.CrossRefGoogle Scholar
  24. 24.
    Joslyn G, Richardson DS, White R, Alber T. Dimer formation by an N-terminal coiled coil in the APC protein. Proc Natl Acad Sci U S A. 1993;90:11109–13.PubMedCrossRefGoogle Scholar
  25. 25.
    Kawasaki Y, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat Cell Biol. 2003;5:211–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Mahmoud NN, Boolbol SK, Bilinski RT, Martucci C, Chadburn A, Bertagnolli MM, et al. Apc gene mutation is associated with a dominant-negative effect upon intestinal cell migration. Cancer Res. 1997;57:5045–50.PubMedGoogle Scholar
  27. 27.
    Munemitsu S, Souza B, Muller O, Albert I, Rubinfeld B, Polakis P, et al. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 1994;54:3676–81.PubMedGoogle Scholar
  28. 28.
    Smith KJ, Levy DB, Maupin P, Pollard TD, Vogelstein B, Kinzler KW, et al. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 1994;54:3672–5.PubMedGoogle Scholar
  29. 29.
    Kroboth K, Newton IP, Kita K, Dikovskaya D, Zumbrunn J, Waterman-Storer CM, et al. Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability. Mol Biol Cell. 2007;18:910–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Nathke I. Cytoskeleton out of the cupboard: colon cancer and cytoskeletal changes induced by loss of APC. Nat Rev Cancer. 2006;6:967–74.PubMedCrossRefGoogle Scholar
  31. 31.
    Laurent-Puig P, Beroud C, Soussi T. APC gene: database of germline and somatic mutations in human tumors and cell lines. Nucleic Acids Res. 1998;26:269–70.PubMedCrossRefGoogle Scholar
  32. 32.
    Crabtree MD, Tomlinson IP, Hodgson SV, Neale K, Phillips RK, Houlston RS, et al. Explaining variation in familial adenomatous polyposis: relationship between genotype and phenotype and evidence for modifier genes. Gut. 2002;51:420–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Samowitz WS, Thliveris A, Spirio LN, White R. Alternatively spliced adenomatous polyposis coli (APC) gene transcripts that delete exons mutated in attenuated APC. Cancer Res. 1995;55:3732–4.PubMedGoogle Scholar
  34. 34.
    Nugent KP, Phillips RK, Hodgson SV, Cottrell S, Smith-Ravin J, Pack K, et al. Phenotypic expression in familial adenomatous polyposis: partial prediction by mutation analysis. Gut. 1994;35:1622–3.PubMedCrossRefGoogle Scholar
  35. 35.
    Bertario L, Russo A, Sala P, Varesco L, Giarola M, Mondini P, et al. Multiple approach to the exploration of genotype–phenotype correlations in familial adenomatous polyposis. J Clin Oncol. 2003;21:1698–707.PubMedCrossRefGoogle Scholar
  36. 36.
    Crabtree MD, Fletcher C, Churchman M, Hodgson SV, Neale K, Phillips RK, et al. Analysis of candidate modifier loci for the severity of colonic familial adenomatous polyposis, with evidence for the importance of the N-acetyl transferases. Gut. 2004;53:271–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Lamlum H, Ilyas M, Rowan A, Clark S, Johnson V, Bell J, et al. The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson’s ‘two-hit’ hypothesis. Nat Med. 1999;5:1071–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Albuquerque C, Breukel C, van der Luijt R, Fidalgo P, Lage P, Stors FJ, et al. The ‘just-right’ signaling model: APC somatic mutations are selected based on a specific level of activation of the beta-catenin signaling cascade. Hum Mol Genet. 2002;11:1549–60.PubMedCrossRefGoogle Scholar
  39. 39.
    Crabtree M, Sieber OM, Lipton L, Hodgson SV, Lamlum H, Thomas HJ, et al. Refining the relation between ‘first hits’ and ‘second hits’ at the APC locus: the ‘loose fit’ model and evidence for differences in somatic mutation spectra among patients. Oncogene. 2003;22:4257–65.PubMedCrossRefGoogle Scholar
  40. 40.
    Groves C, Lamlum H, Crabtree J, Williamson J, Taylor C, Bass S, et al. Mutation cluster region, association between germline and somatic mutations and genotype–phenotype correlation in upper gastrointestinal familial adenomatous polyposis. Am J Pathol. 2002;160:2055–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Schneikert J, Grohmann A, Behrens J. Truncated APC regulates the transcriptional activity of beta-catenin in a cell cycle dependent manner. Hum Mol Genet. 2007;16:199–209.PubMedCrossRefGoogle Scholar
  42. 42.
    Laken SJ, Petersen GM, Gruber C, Oddoux H. Ostrer, Giardiello FM, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet. 1997;17:79–83.PubMedCrossRefGoogle Scholar
  43. 43.
    Woodage T, King SM, Wacholder S, Hartge P, Struewing JP, Peinado MA, et al. The APCI1307K allele and cancer risk in a community-based study of Ashkenazi Jews. Nat Genet. 1998;20:62–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Gryfe R, Di Nicola N, Gallinger S, Redston M. Somatic instability of the APC I1307K allele in colorectal neoplasia. Cancer Res. 1998;58:4040–3.PubMedGoogle Scholar
  45. 45.
    Horii A, Nakatsuru S, Ichii S, Nagase H, Nakamura Y. Multiple forms of the APC gene transcripts and their tissue-specific expression. Hum Mol Genet. 1993;2:283–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res. 2000;60:4366–71.PubMedGoogle Scholar
  47. 47.
    Arnold CN, Goel A, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, et al. APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther. 2004;3:960–4.PubMedCrossRefGoogle Scholar
  48. 48.
    Bai AH, Tong JH, To KF, Chan MW, Man EP, Lo KW, et al. Promoter hypermethylation of tumor-related genes in the progression of colorectal neoplasia. Int J Cancer. 2004;112:846–53.PubMedCrossRefGoogle Scholar
  49. 49.
    Chen J, Rocken C, Lofton-Day C, Schulz HU, Muller O, Kutsner N, et al. Molecular analysis of APC promoter methylation and protein expression in colorectal cancer metastasis. Carcinogenesis. 2005;26:37–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, et al. Inherited variants of MYH associated with somatic G:C–>T:A mutations in colorectal tumors. Nat Genet. 2002;30:227–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Moser AR, Pitot HC, Dove WF. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science. 1990;247:322–4.PubMedCrossRefGoogle Scholar
  52. 52.
    Halberg RB, Katzung DS, Hoff PD, Moser Ar, Cole CE, Lubet RA, et al. Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers. Proc Natl Acad Sci U S A. 2000;97:3461–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Caldwell CM, Green RA, Kaplan KB. APC mutations lead to cytokinetic failures in vitro and tetraploid genotypes in Min mice. J Cell Biol. 2007;178:1109–20.PubMedCrossRefGoogle Scholar
  54. 54.
    Moser AR, Dove WF, Roth KA, Gordon JI. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J Cell Biol. 1992;116:1517–26.PubMedCrossRefGoogle Scholar
  55. 55.
    Boivin GP, Washington K, Yang K, Ward JM, Pretlow TP, Russell R, et al. Pathology of mouse models of intestinal cancer: consensus report and recommendations. Gastroenterology. 2003;124:762–77.PubMedCrossRefGoogle Scholar
  56. 56.
    Dietrich WF, Lander ES, Smith JS, Moser AR, Gould KA, Luongo KA, et al. Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell. 1993;75:631–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Gould K, Luongo AC, Moser AR, McNeley MK, Borenstein N, Shedlovsky A, Dove WF, Hong K, Dietrich WF, Lander ES. Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice. Genetics. 1996;144:1777–85.PubMedGoogle Scholar
  58. 58.
    Gould KA, Dietrich WF, Borenstein N, Lander ES, Dove WF. Mom1 is a semi-dominant modifier of intestinal adenoma size and multiplicity in Min/+ mice. Genetics. 1996;144:1769–76.PubMedGoogle Scholar
  59. 59.
    MacPhee M, Chepenik KP, Liddell RA, Nelson KK, Siracusa LD, Buhberg AM, et al. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. Cell. 1995;81:957–66.PubMedCrossRefGoogle Scholar
  60. 60.
    Coremier RT, Bilger A, Lillich AG, Halberg RB, Hong KA, Gould KA, et al. The MomlAKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. Oncogence. 2000;19:3182-92Google Scholar
  61. 61.
    Tomlinson IP, Beck NE, Neale K, Bodmer WF. Variants at the secretory phospholipase A2 (PLA2G2A) locus: analysis of associations with familial adenomatous polyposis and sporadic colorectal tumours. Ann Hum Genet. 1996;60:369–76.PubMedCrossRefGoogle Scholar
  62. 62.
    Silverman KA, Koratkar R, Siracusa LD, Buchberg AM. Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia. Genome Res. 2002;12:88–97.PubMedCrossRefGoogle Scholar
  63. 63.
    Baran AA, Silverman KA, Zeskand J, Koratkar R, Palmer A, McCullen K, et al. The modifier of Min 2 (Mom2) locus: embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression. Genome Res. 2007;17:566–76.PubMedCrossRefGoogle Scholar
  64. 64.
    Haines J, Johnson V, Pack K, Suraweera N, Slijepcevic P, Cabuy E, et al. Genetic basis of variation in adenoma multiplicity in ApcMin/+ Mom1S mice. Proc Natl Acad Sci U S A. 2005;102:2868–73.PubMedCrossRefGoogle Scholar
  65. 65.
    Kwong LN, Shedlovsky A, Biehl BS, Clipson L, Pasch CA, Dove WF, et al. Identification of Mom7, a novel modifier of Apc(Min/+) on mouse chromosome 18. Genetics. 2007;176:1237–44.PubMedCrossRefGoogle Scholar
  66. 66.
    Taketo MM. Wnt signaling and gastrointestinal tumorigenesis in mouse models. Oncogene. 2006;25:7522–30.PubMedCrossRefGoogle Scholar
  67. 67.
    Colnot S, Niwa-Kawakita M, Hamard G, Godard C, Le Plenier S, Houbron C, et al. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab Invest. 2004;84:1619–30.PubMedCrossRefGoogle Scholar
  68. 68.
    Oshima M, Oshima H, Kitagawa K, Kobayashi M, Itakura C, Taketo M, et al. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci U S A. 1995;92:4482–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Li Q, Ishikawa TO, Oshima M, Taketo MM. The threshold level of adenomatous polyposis coli protein for mouse intestinal tumorigenesis. Cancer Res. 2005;65:8622–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Fodde R, Edelmann W, Yang K, van Leeuwen C, Carlson C, Renault B, et al. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci U S A. 1994;91:8969–73.PubMedCrossRefGoogle Scholar
  71. 71.
    Quesada CF, Kimata H, Mori M, Nishimura M, Tsuneyoshi T, Baba S, et al. Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal adenomas in APC gene 1309 knockout mice. Jpn J Cancer Res. 1998;89:392–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Nagase H, Nakamura Y. Mutations of the APC (adenomatous polyposis coli) gene. Hum Mutat. 1993;2:425–34.PubMedCrossRefGoogle Scholar
  73. 73.
    Rowan AJ, Lamlum H, Ilyas M, Wheeler J, Straub J, Papdopoulou A, et al. APC mutations in sporadic colorectal tumors: A mutational “hotspot” and interdependence of the “two hits”. Proc Natl Acad Sci U S A. 2000;97:3352–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Andreu P, Colnot S, Godard C, Gad S, Chafey P, niwa-Kawakita M, et al. Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development. 2005;132:1443–51.PubMedCrossRefGoogle Scholar
  75. 75.
    Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, et al. Myc deletion rescues Apc deficiency in the small intestine. Nature. 2007;446:676–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Sansom OJ, Reed KR, van de Wetering M, Muncan V, Winton DJ, Clevers H, et al. Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine. J Biol Chem. 2005;280:28463–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Hulit J, Wang C, Li Z, Albanese C, Rao M, DiVisio D, et al. Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice. Mol Cell Biol. 2004;24:7598–611.PubMedCrossRefGoogle Scholar
  78. 78.
    Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995;82:309–19.PubMedCrossRefGoogle Scholar
  79. 79.
    Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell. 1996;85:1125–34.PubMedCrossRefGoogle Scholar
  80. 80.
    Edelmann W, Umar A, Yang K, Heyer J, Kucherlapati M, Lia M, et al. The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Res. 2000;60:803–7.PubMedGoogle Scholar
  81. 81.
    Reitmair AH, Schmits R, Ewel A, Bapat B, Redston M, Mitri A, et al. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet. 1995;11:64–70.PubMedCrossRefGoogle Scholar
  82. 82.
    Baker SM, Harris AC, Tsao JL, Flath TJ, Bronner CE, Gordon M, et al. Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice. Cancer Res. 1998;58:1087–9.PubMedGoogle Scholar
  83. 83.
    Kuraguchi M, Edelmann W, Yang K, Lipkin M, Kucherlapati R, et al. Tumor-associated Apc mutations in Mlh1−/− Apc1638N mice reveal a mutational signature of Mlh1 deficiency. Oncogene. 2000;19:5755–63.PubMedCrossRefGoogle Scholar
  84. 84.
    Reitmair AH, Cai JC, Bjerknes M, Redston M, Cheng H, et al. MSH2 deficiency contributes to accelerated APC-mediated intestinal tumorigenesis. Cancer Res. 1996;56:2922–6.PubMedGoogle Scholar
  85. 85.
    Edelmann W, Yang K, Kuraguchi M, Heyer J, Lia M, et al. Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res. 1999;59:1301–7.PubMedGoogle Scholar
  86. 86.
    Sansom OJ, Meniel V, Wilkins JA, Cole AM, Oien KA, et al. Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proc Natl Acad Sci U S A. 2006;103:14122–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Oshima H, Oshima M, Kobayashi M, Tsutsumi M, Taketo MM. Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice. Cancer Res. 1997;57:1644–9.PubMedGoogle Scholar
  88. 88.
    Smits R, Kartheuser A, Jagmohan-Changur S, Leblanc V, Breukel C, et al. Loss of Apc and the entire chromosome 18 but absence of mutations at the Ras and Tp53 genes in intestinal tumors from Apc1638N, a mouse model for Apc-driven carcinogenesis. Carcinogenesis. 1997;18:321–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Batlle E, Bacani J, Begthel H, Jonkheer S, Gregorieff A, et al. EphB receptor activity suppresses colorectal cancer progression. Nature. 2005;435:1126–30.PubMedCrossRefGoogle Scholar
  90. 90.
    Alberici P, Jagmohan-Changur S, De Pater E, Van Der Valk M, Smits R, et al. Smad4 haploinsufficiency in mouse models for intestinal cancer. Oncogene. 2006;25:1841–51.PubMedCrossRefGoogle Scholar
  91. 91.
    Hamamoto T, Beppu H, Okada H, Kawabata M, Kitamura T, et al. Compound disruption of smad2 accelerates malignant progression of intestinal tumors in apc knockout mice. Cancer Res. 2002;62:5955–61.PubMedGoogle Scholar
  92. 92.
    Takaku K, Oshima M, Miyoshi H, Matsui M, Seldin MF, et al. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Cell. 1998;92:645–56.PubMedCrossRefGoogle Scholar
  93. 93.
    Pretlow TP, Edelmann W, Kucherlapati R, Pretlow TG, Augenlicht LH. Spontaneous aberrant crypt foci in Apc1638N mice with a mutant Apc allele. Am J Pathol. 2003;163:1757–63.PubMedCrossRefGoogle Scholar
  94. 94.
    Smits R, van der Houven van Oordt W, Luz A, Zurcher C, Jagmohan-Changur S, et al. Apc1638N: a mouse model for familial adenomatous polyposis-associated desmoid tumors and cutaneous cysts. Gastroenterology. 1998;114:275–83.PubMedCrossRefGoogle Scholar
  95. 95.
    Shibata H, Toyama K, Shioya H, Ito M, Hirota M, et al. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science. 1997;278:120–3.PubMedCrossRefGoogle Scholar
  96. 96.
    Sasai H, Masaki M, Wakitani K. Suppression of polypogenesis in a new mouse strain with a truncated Apc(Delta474) by a novel COX-2 inhibitor, JTE-522. Carcinogenesis. 2000;21:953–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Luo G, Santoro IM, McDaniel LD, Nishijima I, Mills M, et al. Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nat Genet. 2000;26:424–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Luis G. Carvajal-Carmona
  • Andrew Silver
  • Ian P. Tomlinson
    • 1
    Email author
  1. 1.Molecular and Population Genetics LaboratoryCancer Research UK London Research InstituteLondonUK

Personalised recommendations