Genotype to phenotype: Analyzing the effects of inherited mutations in colorectal cancer families

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volumn 693, Issue 1-2, 2010, Pages 32-45

  Heinen, Christopher D ^a  

^a UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

Author keywords

Colon cancer; Familial adenomatous polyposis; Hereditary non polyposis colon cancer; Mismatch repair; Mutation

Indexed keywords

APC PROTEIN; BETA CATENIN; BONE MORPHOGENETIC PROTEIN 4; CYCLIN D1; GLUTATHIONE TRANSFERASE; GLYCOGEN SYNTHASE KINASE 3BETA; HERMES ANTIGEN; MISMATCH REPAIR PROTEIN; MYC PROTEIN; PROTEIN MSH2; WNT PROTEIN;

CARCINOGENESIS; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE REGULATION; CELL CYCLE S PHASE; CELL MIGRATION; CHROMOSOMAL INSTABILITY; CHROMOSOME ABERRATION; CODON; COLORECTAL CANCER; CYTOGENETICS; DOWN REGULATION; FAMILIAL COLON POLYPOSIS; FRAMESHIFT MUTATION; GENE DISRUPTION; GENE FREQUENCY; GENE FUNCTION; GENE MUTATION; GENE OVEREXPRESSION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HEREDITARY NONPOLYPOSIS COLORECTAL CANCER; HETEROZYGOSITY LOSS; HUMAN; MICROTUBULE; MISSENSE MUTATION; NONHUMAN; PHENOTYPE; PIGMENT EPITHELIUM; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN POLYMORPHISM; PROTEIN PROTEIN INTERACTION; REVIEW; RNA SPLICING; SIGNAL TRANSDUCTION;

ADENOMATOUS POLYPOSIS COLI; COLORECTAL NEOPLASMS; COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS; DNA MISMATCH REPAIR; GENES, APC; GENETIC VARIATION; GENOTYPE; HUMANS; MUTATION; PHENOTYPE;

EID: 78049434369     PISSN: 00275107     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mrfmmm.2009.09.004     Document Type: Review

References (209)

1. Sjoblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314:268-274.
2. Wood L.D., Parsons D.W., Jones S., Lin J., Sjoblom T., Leary R.J., Shen D., Boca S.M., Barber T., Ptak J., Silliman N., Szabo S., Dezso Z., Ustyanksky V., Nikolskaya T., Nikolsky Y., Karchin R., Wilson P.A., Kaminker J.S., Zhang Z., Croshaw R., Willis J., Dawson D., Shipitsin M., Willson J.K.V., Sukumar S., Polyak K., Park B.H., Pethiyagoda C.L., Pant P.V.K., Ballinger D.G., Sparks A.B., Hartigan J., Smith D.R., Suh E., Papadopoulos N., Buckhaults P., Markowitz S.D., Parmigiani G., Kinzler K.W., Velculescu V.E., Vogelstein B. The genomic landscapes of human breast and colorectal cancers. Science 2007, 318:1108-1113.
3. Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 2008, 456:66-72.
4. Ding L., Getz G., Wheeler D.A., Mardis E.R., McLellan M.D., Cibulskis K., Sougnez C., Greulich H., Muzny D.M., Morgan M.B., Fulton L., Fulton R.S., Zhang Q., Wendl M.C., Lawrence M.S., Larson D.E., Chen K., Dooling D.J., Sabo A., Hawes A.C., Shen H., Jhangiani S.N., Lewis L.R., Hall O., Zhu Y., Mathew T., Ren Y., Yao J., Scherer S.E., Clerc K., Metcalf G.A., Ng B., Milosavljevic A., Gonzalez-Garay M.L., Osborne J.R., Meyer R., Shi X., Tang Y., Koboldt D.C., Lin L., Abbott R., Miner T.L., Pohl C., Fewell G., Haipek C., Schmidt H., Dunford-Shore B.H., Kraja A., Crosby S.D., Sawyer C.S., Vickery T., Sander S., Robinson J., Winckler W., Baldwin J., Chirieac L.R., Dutt A., Fennell T., Hanna M., Johnson B.E., Onofrio R.C., Thomas R.K., Tonon G., Weir B.A., Zhao X., Ziaugra L., Zody M.C., Giordano T., Orringer M.B., Roth J.A., Spitz M.R., Wistuba I.I., Ozenberger B., Good P.J., Chang A.C., Beer D.G., Watson M.A., Ladanyi M., Broderick S., Yoshizawa A., Travis W.D., Pao W., Province M.A., Weinstock G.M., Varmus H.E., Gabriel S.B., Lander E.S., Gibbs R.A., Meyerson M., Wilson R.K. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008, 455:1069-1075.
5. Parsons D.W., Jones S., Zhang X., Lin J.C.-H., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.-M., Gallia G.L., Olivi A., McLendon R., Rasheed B.A., Keir S., Nikolskaya T., Nikolsky Y., Busam D.A., Tekleab H., Diaz L.A., Hartigan J., Smith D.R., Strausberg R.L., Marie S.K.N., Shinjo S.M.O., Yan H., Riggins G.J., Bigner D.D., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321:1807-1812.
6. Fearon E.R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990, 61:759-767.
7. Rustgi A. The genetics of hereditary colon cancer. Genes Dev. 2007, 21:2525-2538.
8. Burt R.W. Polyposis syndromes. Textbook of Gastroenterology 1991, vol. 2:1674-1696. J.B. Lippincott Company, Philadelphia.
9. Lynch H.T., Lynch J.F. Genetics of colonic cancer. Digestion 1998, 59:481-492.
10. Fearon E.R., Hamilton S.R., Vogelstein B. Clonal analysis of human colorectal tumors. Science 1987, 238:193-197.
11. Herrera L., Kakati S., Gibas L., Pietrzak E., Sandberg A.A. Gardner syndrome in a man with an interstitial deletion of 5q. Am. J. Med. Genet. 1986, 25:473-476.
12. Bodmer W.F., Bailey C.J., Bodmer J., Bussey H.J., Ellis A., Gorman P., Lucibello F.C., Murday V.A., Rider S.H., Scambler P. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature 1987, 328:614-616.
13. Leppert M., Dobbs M., Scambler P., O'Connell P., Nakamura Y., Stauffer D., Woodward S., Burt R., Hughes J., Gardner E., et al. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 1987, 238:1411-1413.
14. Nakamura Y., Lathrop M., Leppert M., Dobbs M., Wasmuth J., Wolff E., Carlson M., Fujimoto E., Krapcho K., Sears T., et al. Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am. J. Hum. Genet. 1988, 43:638-644.
15. Joslyn G., Carlson M., Thliveris A., Albertsen H., Gelbert L., Samowitz W., Groden J., Stevens J., Spirio L., Robertson M. Identification of deletion mutations and three new genes at the familial polyposis locus. Cell 1991, 66:601-613.
16. Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991, 66:589-600.
17. Powell S.M., Zilz N., Beazer-Barclay Y., Bryan T.M., Hamilton S.R., Thibodeau S.N., Vogelstein B., Kinzler K.W. APC mutations occur early during colorectal tumorigenesis. Nature 1992, 359:235-237.
18. Smith K.J., Johnson K.A., Bryan T.M., Hill D.E., Markowitz S., Willson J.K., Paraskeva C., Petersen G.M., Hamilton S.R., Vogelstein B. The APC gene product in normal and tumor cells. Proc. Natl. Acad. Sci. U.S.A. 1993, 90:2846-2850.
19. Jass J., Whitehall V., Young J., Leggett B. Emerging concepts in colorectal neoplasia. Gastroenterology 2002, 123:862-876.
20. Tanaka K., Oshimura M., Kikuchi R., Seki M., Hayashi T., Miyaki M. Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. Nature 1991, 349:340-342.
21. Goyette M.C., Cho K., Fasching C.L., Levy D.B., Kinzler K.W., Paraskeva C., Vogelstein B., Stanbridge E.J. Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer. Mol. Cell Biol. 1992, 12:1387-1395.
22. Groden J., Joslyn G., Samowitz W., Jones D., Bhattacharyya N., Spirio L., Thliveris A., Robertson M., Egan S., Meuth M. Response of colon cancer cell lines to the introduction of APC, a colon-specific tumor suppressor gene. Cancer Res. 1995, 55:1531-1539.
23. Rubinfeld B., Souza B., Albert I., Muller O., Chamberlain S.H., Masiarz F.R., Munemitsu S., Polakis P. Association of the APC gene product with beta-catenin. Science 1993, 262:1731-1734.
24. Su L.K., Vogelstein B., Kinzler K.W. Association of the APC tumor suppressor protein with catenins. Science 1993, 262:1734-1737.
25. Peifer M., Sweeton D., Casey M., Wieschaus E. Wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Development 1994, 120:369-380.
26. Funayama N., Fagotto F., McCrea P., Gumbiner B.M. Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. J. Cell Biol. 1995, 128:959-968.
27. McMahon A.P., Moon R.T. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell 1989, 58:1075-1084.
28. Behrens J., von Kries J.P., Kuhl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 1996, 382:638-642.
29. Molenaar M., van de Wetering M., Oosterwegel M., Peterson-Maduro J., Godsave S., Korinek V., Roose J., Destree O., Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell 1996, 86:391-399.
30. He T.C., Sparks A.B., Rago C., Hermeking H., Zawel L., da Costa L.T., Morin P.J., Vogelstein B., Kinzler K.W. Identification of c-MYC as a target of the APC pathway. Science 1998, 281:1509-1512.
31. Tetsu O., McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999, 398:422-426.
32. van de Wetering M., Sancho E., Verweij C., de Lau W., Oving I., Hurlstone A., van der Horn K., Batlle E., Coudreuse D., Haramis A.P., Tjon-Pon-Fong M., Moerer P., van den Born M., Soete G., Pals S., Eilers M., Medema R., Clevers H. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 2002, 111:241-250.
33. Munemitsu S., Albert I., Souza B., Rubinfeld B., Polakis P. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli, (APC) tumor-suppressor protein. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:3046-3050.
34. Korinek V., Barker N., Morin P.J., van Wichen D., de Weger R., Kinzler K.W., Vogelstein B., Clevers H. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science 1997, 275:1784-1787.
35. Rubinfeld B., Albert I., Porfiri E., Fiol C., Munemitsu S., Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996, 272:1023-1026.
36. Neufeld K.L., Zhang F., Cullen B.R., White R.L. APC-mediated downregulation of beta-catenin activity involves nuclear sequestration and nuclear export. EMBO Rep. 2000, 1:519-523.
37. Sierra J., Yoshida T., Joazeiro C.A., Jones K.A. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 2006, 20:586-600.
38. Wong M.H., Hermiston M.L., Syder A.J., Gordon J.I. Forced expression of the tumor suppressor adenomatosis polyposis coli protein induces disordered cell migration in the intestinal epithelium. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:9588-9593.
39. Sansom O.J., Reed K.R., Hayes A.J., Ireland H., Brinkmann H., Newton I.P., Batlle E., Simon-Assmann P., Clevers H., Nathke I.S., Clarke A.R., Winton D.J. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 2004, 18:1385-1390.
40. Nathke I.S., Adams C.L., Polakis P., Sellin J.H., Nelson W.J. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J. Cell Biol. 1996, 134:165-179.
41. Kroboth K., Newton I.P., Kita K., Dikovskaya D., Zumbrunn J., Waterman-Storer C.M., Nathke I.S. Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability. Mol. Biol. Cell 2007, 18:910-918.
42. Su L.K., Burrell M., Hill D.E., Gyuris J., Brent R., Wiltshire R., Trent J., Vogelstein B., Kinzler K.W. APC binds to the novel protein EB1. Cancer Res. 1995, 55:2972-2977.
43. Morrison E.E., Wardleworth B.N., Askham J.M., Markham A.F., Meredith D.M. EB1, a protein which interacts with the APC tumour suppressor, is associated with the microtubule cytoskeleton throughout the cell cycle. Oncogene 1998, 17:3471-3477.
44. Kawasaki Y., Senda T., Ishidate T., Koyama R., Morishita T., Iwayama Y., Higuchi O., Akiyama T. Asef, a link between the tumor suppressor APC and G-protein signaling. Science 2000, 289:1194-1197.
45. Kawasaki Y., Sagara M., Shibata Y., Shirouzu M., Yokoyama S., Akiyama T. Identification and characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42. Oncogene 2007, 26:7620-7627.
46. Hamann M.J., Lubking C.M., Luchini D.N., Billadeau D.D. Asef2 functions as a Cdc42 exchange factor and is stimulated by the release of an autoinhibitory module from a concealed C-terminal activation element. Mol. Cell. Biol. 2007, 27:1380-1393.
47. Kawasaki Y., Sato R., Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat. Cell Biol. 2003, 5:211-215.
48. Watanabe T., Wang S., Noritake J., Sato K., Fukata M., Takefuji M., Nakagawa M., Izumi N., Akiyama T., Kaibuchi K. Interaction with IQGAP1 Links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration. Dev. Cell 2004, 7:871-883.
49. Lengauer C., Kinzler K.W., Vogelstein B. Genetic instabilities in human cancers. Nature 1998, 396:643-649.
50. Fodde R., Kuipers J., Rosenberg C., Smits R., Kielman M., Gaspar C., van Es J.H., Breukel C., Wiegant J., Giles R.H., Clevers H. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat. Cell Biol. 2001, 3:433-438.
51. Dikovskaya D., Schiffmann D., Newton I.P., Oakley A., Kroboth K., Sansom O., Jamieson T.J., Meniel V., Clarke A., Nathke I.S. Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. J. Cell Biol. 2007, 176:183-195.
52. Draviam V.M., Shapiro I., Aldridge B., Sorger P.K. Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cells. EMBO J. 2006, 25:2814-2827. (Epub 2006 Jun 8).
53. 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, 26:269-270.
54. Miyoshi Y., Nagase H., Ando H., Horii A., Ichii S., Nakatsuru S., Aoki T., Miki Y., Mori T., Nakamura Y. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum. Mol. Genet. 1992, 1:229-233.
55. Powell S.M., Petersen G.M., Krush A.J., Booker S., Jen J., Giardiello F.M., Hamilton S.R., Vogelstein B., Kinzler K.W. Molecular diagnosis of familial adenomatous polyposis. NE J. Med. 1993, 329:1982-1987.
56. Nugent K.P., Phillips R.K., Hodgson S.V., Cottrell S., Smith-Ravin J., Pack K., Bodmer W.F. Phenotypic expression in familial adenomatous polyposis: partial prediction by mutation analysis. Gut 1994, 35:1622-1623.
57. Nieuwenhuis M.H., Vasen H.F.A. Correlations between mutation site in APC and phenotype of familial adenomatous polyposis, (FAP): a review of the literature. Crit. Rev. Oncol./Hematol. 2007, 61:153-161.
58. Lamlum H., Ilyas M., Rowan A., Clark S., Johnson V., Bell J., Frayling I., Efstathiou J., Pack K., Payne S., Roylance R., Gorman P., Sheer D., Neale K., Phillips R., Talbot I., Bodmer W., Tomlinson I. 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, 5:1071-1075.
59. Albuquerque C., Breukel C., van der Luijt R., Fidalgo P., Lage P., Slors F.J.M., Leitao C.N., Fodde R., Smits R. 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, 11:1549-1560.
60. Crabtree M., Sieber O.M., Lipton L., Hodgson S.V., Lamlum H., Thomas H.J.W., Neale K., Phillips R.K.S., Heinimann K., Tomlinson I.P.M. 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, 22:4257-4265.
61. 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, 57:4624-4630.
62. Henderson B.R. Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover. Nat. Cell Biol. 2000, 2:653-660.
63. Spirio L., Olschwang S., Groden J., Robertson M., Samowitz W., Joslyn G., Gelbert L., Thliveris A., Carlson M., Otterud B. Alleles of the APC gene: an attenuated form of familial polyposis. Cell 1993, 75:951-957.
64. Soravia C., Berk T., Madlensky L., Mitri A., Cheng H., Gallinger S., Cohen Z., Bapat B. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am. J. Hum. Genet. 1998, 62:1290-1301.
65. Friedl W., Meuschel S., Caspari R., Lamberti C., Krieger S., Sengteller M., Propping P. Attenuated familial adenomatous polyposis due to a mutation in the 3' part of the APC gene. A clue for understanding the function of the APC protein. Hum. Genet. 1996, 97:579-584.
66. Dobbie Z., Spycher M., Hurliman R., Ammann R., Ammann T., Roth J., Muller A., Muller H., Scott R.J. Mutational analysis of the first 14 exons of the adenomatous polyposis coli, (APC) gene. Eur. J. Cancer 1994, 30A:1709-1713.
67. Samowitz W.S., Thliveris A., Spirio L.N., White R. Alternatively spliced adenomatous polyposis coli, (APC) gene transcripts that delete exons mutated in attenuated APC. Cancer Res. 1995, 55:3732-3734.
68. Heppner Goss K., Trzepacz C., Tuohy T.M.F., Groden J. Attenuated APC alleles produce functional protein from internal translation initiation. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:8161-8166.
69. Knudsen A.L., Bisgaard M.L., Bulow S. Attenuated familial adenomatous polyposis, (AFAP). A review of the literature. Fam. Cancer 2003, 2:43-55.
70. van der Luijt R.B., Meera Khan P., Vasen H.F., Breukel C., Tops C.M., Scott R.J., Fodde R. Germline mutations in the 3' part of APC exon 15 do not result in truncated proteins and are associated with attenuated adenomatous polyposis coli. Hum. Genet. 1996, 98:727-734.
71. Gebert J.F., Dupon C., Kadmon M., Hahn M., Herfarth C., von Knebel Doeberitz M., Schackert H.K. Combined molecular and clinical approaches for the identification of families with familial adenomatous polyposis coli. Ann. Surg. 1999, 229:350-361.
72. Spirio L., Green J., Robertson J., Robertson M., Otterud B., Sheldon J., Howse E., Green R., Groden J., White R., Leppert M. The identical 5' splice-site acceptor mutation in five attenuated APC families from Newfoundland demonstrates a founder effect. Hum. Genet. 1999, 105:388-398.
73. Brensinger J.D., Laken S.J., Luce M.C., Powell S.M., Vance G.H., Ahnen D.J., Petersen G.M., Hamilton S.R., Giardiello F.M. Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. Gut 1998, 43:548-552.
74. David S.S., Williams S.D. Chemistry of glycosylases and endonucleases involved in base-excision repair. Chem. Rev. 1998, 98:1221-1262.
75. Al-Tassan N., Chmiel N.H., Maynard J., Fleming N., Livingston A.L., Williams G.T., Hodges A.K., Davies D.R., David S.S., Sampson J.R., Cheadle J.P. Inherited variants of MYH associated with somatic G:C-T: a mutations in colorectal tumors. Nat. Genet. 2002, 30:227-232.
76. Cheadle J.P., Sampson J.R. MUTYH-associated polyposis-from defect in base excision repair to clinical genetic testing. DNA Repair 2007, 6:274-279.
77. Poulsen M., Bisgaard M.L. MUTYH associated polyposis, (MAP). Curr. Genomics 2008, 9:420-435.
78. Laken S.J., Petersen G.M., Gruber S.B., Oddoux C., Ostrer H., Giardiello F.M., Hamilton S.R., Hampel H., Markowitz A., Klimstra D., Jhanwar S., Winawer S., Offit K., Luce M.C., Kinzler K.W., Vogelstein B. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat. Genet. 1997, 17:79-83.
79. Lamlum H., Al Tassan N., Jaeger E., Frayling I., Sieber O., Reza F.B., Eckert M., Rowan A., Barclay E., Atkin W., Williams C., Gilbert J., Cheadle J., Bell J., Houlston R., Bodmer W., Sampson J., Tomlinson I. Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. Hum. Mol. Genet. 2000, 9:2215-2221.
80. Frayling I.M., Beck N.E., Ilyas M., Dove-Edwin I., Goodman P., Pack K., Bell J.A., Williams C.B., Hodgson S.V., Thomas H.J., Talbot I.C., Bodmer W.F., Tomlinson I.P. The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:10722-10727.
81. Cleary S., Kim H., Croitoru M., Redston M., Knight J., Gallinger S., Gryfe R. Missense polymorphisms in the adenomatous polyposis coli gene and colorectal cancer risk. Dis. Colon Rectum 2008, 51:1467-1473.
82. Hahnloser D., Petersen G.M., Rabe K., Snow K., Lindor N.M., Boardman L., Koch B., Doescher D., Wang L., Steenblock K., Thibodeau S.N. The APC E1317Q variant in adenomatous polyps and colorectal cancers. Cancer Epidemiol. Biomarkers Prev. 2003, 12:1023-1028.
83. Gryfe R., Di Nicola N., Gallinger S., Redston M. Somatic instability of the APC I1307K allele in colorectal neoplasia. Cancer Res. 1998, 58:4040-4043.
84. Sieber O., Lara Lipton K.H., Tomlinson I. Colorectal tumourigenesis in carriers of the APC I1307K variant: lone gunman or conspiracy?. J. Pathol. 2003, 199:137-139.
85. Wallis Y., Morton D., McKeown C., Macdonald F. Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition. J. Med. Genet. 1999, 36:14-20.
86. Menéndez M., González S., Obrador-Hevia A., Domínguez A., Pujol M.J., Valls J., Canela N., Blanco I., Torres A., Pineda-Lucena A., Moreno V., Bachs O., Capellá G. Functional characterization of the novel APC N1026S variant associated with attenuated familial adenomatous polyposis. Gastroenterology 2008, 134:56-64.
87. Zhou X.-L., Eriksson U., Werelius B., Kressner U., Sun X.-F., Lindblom A. Definition of candidate low risk APC alleles in a Swedish population. Int. J. Cancer 2004, 110:550-557.
88. Cartegni L., Chew S.L., Krainer A.R. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet. 2002, 3:285-298.
89. Aretz S., Siegfried Uhlhaas Y.S., Constanze P., Elisabeth M., Reiner C., Gabriela M., Karsten S., Peter P., Waltraut F. Familial adenomatous polyposis: aberrant splicing due to missense or silent mutations in the APC gene. Hum. Mutat. 2004, 24:370-380.
90. Kaufmann A., Vogt S., Uhlhaas S., Stienen D., Kurth I., Hameister H., Mangold E., Kotting J., Kaminsky E., Propping P., Friedl W., Aretz S. Analysis of rare APC variants at the mRNA level: six pathogenic mutations and literature review. J. Mol. Diagn. 2009, 11:131-139.
91. Eklof Spink K., Fridman S.G., Weis W.I. Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex. EMBO J. 2001, 20:6203-6212.
92. Nathke I.S. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Ann. Rev. Cell Develop. Biol. 2004, 20:337-366.
93. Heinen C.D., Goss K., Cornelius J., Babcock G., Knudsen E., Kowalik T., Groden J. The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway. Gastroenterology 2002, 123:751-763.
94. Faux M.C., Ross J.L., Meeker C., Johns T., Ji H., Simpson R.J., Layton M.J., Burgess A.W. Restoration of full-length adenomatous polyposis coli, (APC) protein in a colon cancer cell line enhances cell adhesion. J. Cell Sci. 2004, 117:427-439.
95. Morin P.J., Vogelstein B., Kinzler K.W. Apoptosis and APC in colorectal tumorigenesis. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:7950-7954.
96. Taketo M., Edelmann W. Mouse models of colon cancer. Gastroenterology 2009, 136:780-798.
97. Moser A.R., Pitot H.C., Dove W.F. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 1990, 247:322-324.
98. Su L.K., Kinzler K.W., Vogelstein B., Preisinger A.C., Moser A.R., Luongo C., Gould K.A., Dove W.F. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 1992, 256:668-670.
99. Oshima M., Oshima H., Kitagawa K., Kobayashi M., Itakura C., Taketo M. 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, 92:4482-4486.
100. Fodde R., Edelmann W., Yang K., van Leeuwen C., Carlson C., Renault B., Breukel C., Alt E., Lipkin M., Khan P.M. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:8969-8973.
101. Colnot S., Niwa-Kawakita M., Hamard G., Godard C., Le Plenier S., Houbron C., Romagnolo B., Berrebi D., Giovannini M., Perret C. Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers. Lab Invest. 2004, 84:1619-1630.
102. Hinoi T., Akyol A., Theisen B.K., Ferguson D.O., Greenson J.K., Williams B.O., Cho K.R., Fearon E.R. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res. 2007, 67:9721-9730.
103. Lynch H.T., Lynch J., Shaw T., Lubinski J. HNPCC, (Lynch syndrome): differential diagnosis, molecular genetics and management-a review. Hereditary Cancer Clin. Practice 2003, 1:7-18.
104. Vasen H.F., Mecklin J.P., Khan P.M., Lynch H.T. The international collaborative group on hereditary non-polyposis colorectal cancer, (ICG-HNPCC). Dis. Colon Rectum 1991, 34:424-425.
105. Rodriguez-Bigas M., Boland C., Hamilton S., Henson D., Jass J., Khan P., Lynch H., Perucho M., Smyrk T., Sobin L., Srivastava S. A national cancer institute workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. J. Natl. Cancer Inst. 1997, 89:1758-1762.
106. Umar A., Boland C.R., Terdiman J.P., Syngal S., Chapelle A.D.L., Ruschoff J., Fishel R., Lindor N.M., Burgart L.J., Hamelin R., Hamilton S.R., Hiatt R.A., Jass J., Lindblom A., Lynch H.T., Peltomaki P., Ramsey S.D., Rodriguez-Bigas M.A., Vasen H.F.A., Hawk E.T., Barrett J.C., Freedman A.N., Srivastava S. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer, (Lynch syndrome) and microsatellite instability. J. Natl. Cancer Inst. 2004, 96:261-268.
107. Liu B., Parsons R., Papadopoulos N., Nicolaides N.C., Lynch H.T., Watson P., Jass J.R., Dunlop M., Wyllie A., Peltomaki P., de la Chapelle A., Hamilton S.R., Vogelstein B., Kinzler K.W. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat. Med. 1996, 2:169-174.
108. Strand M., Prolla T.A., Liskay R.M., Petes T.D. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 1993, 365:274-276.
109. Heinen C.D., Richardson D., White R., Groden J. Microsatellite instability in colorectal adenocarcinoma cell lines that have full-length adenomatous polyposis coli protein. Cancer Res. 1995, 55:4797-4799.
110. Salahshor S., Kressner U., Pahlman L., Glimelius B., Lindmark G., Lindblom A. Colorectal cancer with and without microsatellite instability involves different genes. Genes Chromosomes Cancer 1999, 26:247-252.
111. Jass J., Biden K., Cummings M., Simms L., Walsh M., Schoch E., Meltzer S., Wright C., Searle J., Young J., Leggett B. Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways. J. Clin. Pathol. 1999, 52:455-460.
112. Fishel R., Lescoe M.K., Rao M.R., Copeland N.G., Jenkins N.A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 1993, 75:1027-1038.
113. Leach F.S., Nicolaides N.C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomaki P., Sistonen P., Aaltonen L.A., Nystrom-Lahti M., et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 1993, 75:1215-1225.
114. Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K., Kane M., Earabino C., Lipford J., Lindblom A., et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994, 368:258-261.
115. Papadopoulos N., Nicolaides N.C., Wei Y.F., Ruben S.M., Carter K.C., Rosen C.A., Haseltine W.A., Fleischmann R.D., Fraser C.M., Adams M.D., et al. Mutation of a mutL homolog in hereditary colon cancer. Science 1994, 263:1625-1629.
116. Peltomaki P., Vasen H.F. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology 1997, 113:1146-1158.
117. Kolodner R.D., Tytell J.D., Schmeits J.L., Kane M.F., Gupta R.D., Weger J., Wahlberg S., Fox E.A., Peel D., Ziogas A., Garber J.E., Syngal S., Anton-Culver H., Li F.P. Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999, 59:5068-5074.
118. Nicolaides N.C., Papadopoulos N., Liu B., Wei Y.F., Carter K.C., Ruben S.M., Rosen C.A., Haseltine W.A., Fleischmann R.D., Fraser C.M., et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 1994, 371:75-80.
119. Worthley D.L., Walsh M.D., Barker M., Ruszkiewicz A., Bennett G., Phillips K., Suthers G. Familial mutations in PMS2 can cause autosomal dominant hereditary nonpolyposis colorectal cancer. Gastroenterology 2005, 128:1431-1436.
120. Ricciardone M.D., Ozcelik T., Cevher B., Ozdag H., Tuncer M., Gurgey A., Uzunalimoglu O., Cetinkaya H., Tanyeli A., Erken E., Ozturk M. Human MLH1 deficiency predisposes to hematological maligancy and neurofibromatosis type 1. Cancer Res. 1999, 59:290-293.
121. Edelmann L., Edelmann W. Loss of DNA mismatch repair function and cancer predisposition in the mouse: animal models for human hereditary nonpolyposis colorectal cancer. Am. J. Med. Genet. C: Semin. Med. Genet. 2004, 129:91-99.
122. Wang Q., Lasset C., Desseigne F., Frappaz D., Bergeron C., Navarro C., Ruano E., Puisieux A. Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Res. 1999, 59:294-297.
123. Whiteside D., McLeod R., Graham G., Steckley J.L., Booth K., Somerville M.J., Andrew S.E. A Homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple Cafe-au-Lait Spots. Cancer Res. 2002, 62:359-362.
124. Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam. Cancer 2005, 4:323-333.
125. Poley J.-W.A.W., Monique M., Hoogmans C.P., Fred H., Menko C., Tops T., Kros Johan, M., Reddingius Roel E., Meijers-Heijboer H., Kuipers Ernst J., Dinjens Winand N.M. Biallelic germline mutations of mismatch-repair genes. Cancer 2007, 109:2349-2356. on behalf of the Rotterdam Initiative on Gastrointestinal Hereditary Tumors.
126. Hartmann A., Zanardo L., Bocker-Edmonston T., Blaszyk H., Dietmaier W., Stoehr R., Cheville J.C., Junker K., Wieland W., Knuechel R., Rueschoff J., Hofstaedter F., Fishel R. Frequent microsatellite instability in sporadic tumors of the upper urinary tract. Cancer Res. 2002, 62:6796-6802.
127. Risinger J.I., Berchuck A., Kohler M.F., Watson P., Lynch H.T., Boyd J. Genetic instability of microsatellites in endometrial carcinoma. Cancer Res. 1993, 53:5100-5103.
128. Simpkins S.B., Bocker T., Swisher E.M., Mutch D.G., Gersell D.J., Kovatich A.J., Palazzo J.P., Fishel R., Goodfellow P.J. MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers. Hum. Mol. Genet. 1999, 8:661-666.
129. Dietmaier W., Wallinger S., Bocker T., Kullmann F., Fishel R., Ruschoff J. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res. 1997, 57:4749-4756.
130. Cunningham J., Christensen E., Tester D., Kim C., Roche P., Burgart L., Thibodeau S. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res. 1998, 58:3455-3460.
131. Herman J.G., Umar A., Polyak K., Graff J.R., Ahuja N., Issa J.-P.J., Markowitz S., Willson J.K.V., Hamilton S.R., Kinzler K.W., Kane M.F., Kolodner R.D., Vogelstein B., Kunkel T.A., Baylin S.B. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:6870-6875.
132. Kane M., Loda M., Gaida G., Lipman J., Mishra R., Goldman H., Jessup J., Kolodner R. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997, 57:808-811.
133. Thibodeau S.N., French A.J., Roche P.C., Cunningham J.M., Tester D.J., Lindor N.M., Moslein G., Baker S.M., Liskay R.M., Burgart L.J., Honchel R., Halling K.C. Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes. Cancer Res. 1996, 56:4836-4840.
134. Imai K., Yamamoto H. Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 2008, 29:673-680.
135. Jass J.R. Serrated route to colorectal cancer: back street or super highway?. J. Pathol. 2001, 193:283-285.
136. Fishel R., Kolodner R.D. Identification of mismatch repair genes and their role in the development of cancer. Curr. Opin. Genet. Dev. 1995, 5:382-395.
137. Loeb L.A., Springgate C.F., Battula N. Errors in DNA replication as a basis of malignant changes. Cancer Res. 1974, 34:2311-2321.
138. Markowitz S., Wang J., Myeroff L., Parsons R., Sun L., Lutterbaugh J., Fan R.S., Zborowska E., Kinzler K.W., Vogelstein B., Brattain M., Willson J.K.V. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995, 268:1336-1338.
139. Duval A., Hamelin R. Mutations at coding repeat sequences in mismatch repair-deficient human cancers: toward a new concept of target genes for instability. Cancer Res. 2002, 62:2447-2454.
140. Toft N.J., Winton D.J., Kelly J., Howard L.A., Dekker M., te Riele H., Arends M.J., Wyllie A.H., Margison G.P., Clarke A.R. Msh2 status modulates both apoptosis and mutation frequency in the murine small intestine. Proc. Natl. Acad. Sci. U.S.A. 1999, 96:3911-3915.
141. Wu J., Gu L., Wang H., Geacintov N.E., Li G.M. Mismatch repair processing of carcinogen-DNA adducts triggers apoptosis. Mol. Cell Biol. 1999, 19:8292-8301.
142. Zhang H., Richards B., Wilson T., Lloyd M., Cranston A., Thorburn A., Fishel R., Meuth M. Apoptosis induced by overexpression of hMSH2 or hMLH1. Cancer Res. 1999, 59:3021-3027.
143. de Wind N., Dekker M., van Rossum A., van der Valk M., te Riele H. Mouse models for hereditary nonpolyposis colorectal cancer. Cancer Res. 1998, 58:248-255.
144. Davis T.W., Wilson-Van Patten C., Meyers M., Kunugi K.A., Cuthill S., Reznikoff C., Garces C., Boland C.R., Kinsella T.J., Fishel R., Boothman D.A. Defective expression of the DNA mismatch repair protein, MLH1, alters G2-M cell cycle checkpoint arrest following ionizing radiation. Cancer Res. 1998, 58:767-778.
145. Hickman M.J., Samson L.D. Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Proc. Natl. Acad. Sci. U.S.A. 1999, 96:10764-10769.
146. Yan T., Schupp J.E., Hwang H.-s., Wagner M.W., Berry S.E., Strickfaden S., Veigl M.L., Sedwick W.D., Boothman D.A., Kinsella T.J. Loss of DNA mismatch repair imparts defective cdc2 signaling and G2 arrest responses without altering survival after ionizing radiation. Cancer Res. 2001, 61:8290-8297.
147. Lan Z., Sever-Chroneos Z., Strobeck M.W., Park C.H., Baskaran R., Edelmann W., Leone G., Knudsen E.S. DNA-damage invokes mismatch repair dependent cyclin D1 attenuation and RB signaling pathways to inhibit CDK2. J. Biol. Chem. 2002, 277:8372-8381.
148. Cejka P., Stojic L., Mojas N., Russell A.M., Heinimann K., Cannavo E., di Pietro M., Marra G., Jiricny J. Methylation-induced G2/M arrest requires a full complement of the mismatch repair protein hMLH1. EMBO J. 2003, 22:2245-2254.
149. Stojic L., Mojas N., Cejka P., di Pietro M., Ferrari S., Marra G., Jiricny J. Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase. Genes Dev. 2004, 18:1331-1344.
150. Jiricny J. The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 2006, 7:335-346.
151. Fishel R. Signaling mismatch repair in cancer. Nat. Med. 1999, 5:1239-1241.
152. Heinen C.D., Schmutte C., Fishel R. DNA repair and tumorigenesis: lessons from hereditary cancer syndromes. Cancer Biol. Therapy 2002, 1:477-485.
153. Lin D.P., Wang Y., Scherer S.J., Clark A.B., Yang K., Avdievich E., Jin B., Werling U., Parris T., Kurihara N., Umar A., Kucherlapati R., Lipkin M., Kunkel T.A., Edelmann W. An Msh2 point mutation uncouples DNA mismatch repair and apoptosis. Cancer Res. 2004, 64:517-522.
154. Yang G., Scherer S.J., Shell S.S., Yang K., Kim M., Lipkin M., Kucherlapati R., Kolodner R.D., Edelmann W. Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell 2004, 6:139-150.
155. Carethers J.M., Smith E.J., Behling C.A., Nguyen L., Tajima A., Doctolero R.T., Cabrera B.L., Goel A., Arnold C.A., Miyai K., Boland C.R. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 2004, 126:394-401.
156. Ribic C.M., Sargent D.J., Moore M.J., Thibodeau S.N., French A.J., Goldberg R.M., Hamilton S.R., Laurent-Puig P., Gryfe R., Shepherd L.E., Tu D., Redston M., Gallinger S. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N. Engl. J. Med. 2003, 349:247-257.
157. Watanabe Y., Koi M., Hemmi H., Hoshai H., Noda K. A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer. Br. J. Cancer 2001, 85:1064-1069.
158. Marcelis C.L.M., van der Putten H.W.H.M., Tops C., Lutgens L.C.H.W., Moog U. Chemotherapy resistant ovarian cancer in carriers of an hMSH2 mutation?. Fam. Cancer 2001, 1:109-111.
159. Harfe B.D., Jinks-Robertson S. DNA mismatch repair and genetic instability. Annu. Rev. Genet. 2000, 34:359-399.
160. Reenan R., Kolodner R.D. Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Genetics 1992, 132:975-985.
161. Alani E., Reenan R., Kolodner R.D. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics 1994, 137:19-39.
162. Prolla T.A., Christie D.M., Liskay R.M. Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene. Mol. Cell. Biol. 1994, 14:407-415.
163. Rayssiguier C., Thaler D.S., Radman M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 1989, 342:396-401.
164. Rizki A., Lundblad V. Defects in mismatch repair promote telomerase-independent proliferation. Nature 2001, 411:713-716.
165. Baker S.M., PlugAnnemieke W., Prolla T.A., Bronner C.E., Harris A.C., Yao X., Christie D.-M., Monell C., Arnheim N., Bradley A., Ashley T., Liskay R.M. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat. Genet. 1996, 13:336-342.
166. Edelmann W., Cohen P.E., Kane M., Lau K., Morrow B., Bennett S., Umar A., Kunkel T., Cattoretti G., Chaganti R., Pollard J.W., Kolodner R.D., Kucherlapati R. Meiotic pachytene arrest in MLH1-deficient mice. Cell 1996, 85:1125-1134.
167. Hunter N., Borts R.H. Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Genes Dev. 1997, 11:1573-1582.
168. Wang T.-F., Kleckner N., Hunter N. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proc. Natl. Acad. Sci. U.S.A. 1999, 96:13914-13919.
169. Cascalho M., Wong J., Steinberg C., Wabl M. Mismatch repair co-opted by hypermutation. Science 1998, 279:1207-1210.
170. Martin A., Scharff M.D. AID and mismatch repair in antibody diversification. Nat. Rev. Immunol. 2002, 2:605-614.
171. Schanz S., Castor D., Fischer F., Jiricny J. Interference of mismatch and base excision repair during the processing of adjacent U/G mispairs may play a key role in somatic hypermutation. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:5593-5598.
172. Stavnezer J., Schrader C.E. Mismatch repair converts AID-instigated nicks to double-strand breaks for antibody class-switch recombination. Trends Genet. 2006, 22:23-28.
173. Warren J.J., Pohlhaus T.J., Changela A., Iyer R.R., Modrich P.L., Beese L.S. Structure of the human MutSalpha DNA lesion recognition complex. Mol. Cell 2007, 26:579-592.
174. Ban C., Yang W. Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis. Cell 1998, 95:541-552.
175. Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. the utility of immunohistochemistry. J. Mol. Diagn. 2008, 10:293-300.
176. Berends M.J., Wu Y., Sijmons R.H., Mensink R.G., van der Sluis T., Hordijk-Hos J.M., de Vries E.G., Hollema H., Karrenbeld A., Buys C.H., van der Zee A.G., Hofstra R.M., Kleibeuker J.H. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am. J. Hum. Genet. 2002, 70:26-37.
177. Clark A.B., Cook M.E., Tran H.T., Gordenin D.A., Resnick M.A., Kunkel T.A. Functional analysis of human MutSalpha and MutSbeta complexes in yeast. Nucleic Acids Res. 1999, 27:736-742.
178. Shimodaira H., Filosi N., Shibata H., Suzuki T., Radice P., Kanamaru R., Friend S.H., Kolodner R.D., Ishioka C. Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nat. Genet. 1998, 19:384-389.
179. Polaczek P., Putzke A.P., Leong K., Bitter G.A. Functional genetic tests of DNA mismatch repair protein activity in Saccharomyces cerevisiae. Gene 1998, 213:159-167.
180. Drotschmann K., Clark A.B., Kunkel T.A. Mutator phenotypes of common polymorphisms and missense mutations in MSH2. Curr. Biol. 1999, 9:907-910.
181. Gammie A.E., Erdeniz N., Beaver J., Devlin B., Nanji A., Rose M.D. Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Genetics 2007, 177:707-721.
182. Wanat J.J., Singh N., Alani E. The effect of genetic background on the function of Saccharomyces cerevisiae mlh1 alleles that correspond to HNPCC missense mutations. Hum. Mol. Genet. 2007, 16:445-452.
183. Trojan J., Zeuzem S., Randolph A., Hemmerle C., Brieger A., Raedle J., Plotz G., Jiricny J., Marra G. Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. Gastroenterology 2002, 122:211-219.
184. Thomas D., Roberts J., Kunkel T. Heteroduplex repair in extracts of human HeLa cells. J. Biol. Chem. 1991, 266:3744-3751.
185. Takahashi M., Shimodaira H., Andreutti-Zaugg C., Iggo R., Kolodner R.D., Ishioka C. Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays. Cancer Res. 2007, 67:4595-4604.
186. Ollila S., Sarantaus L., Kariola R., Chan P., Hampel H., Holinski-Feder E., Macrae F., Kohonen-Corish M., Gerdes A.-M., Peltomäki P., Mangold E., de la Chapelle A., Greenblatt M., Nyström M. Pathogenicity of MSH2 missense mutations is typically associated with impaired repair capability of the mutated protein. Gastroenterology 2006, 131:1408-1417.
187. Holmes J., Clark S., Modrich P. Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines. Proc. Natl. Acad. Sci. U.S.A. 1990, 87:5837-5841.
188. Knudsen N.O., Nielsen F.C., Vinther L., Bertelsen R., Holten-Andersen S., Liberti S.E., Hofstra R., Kooi K., Rasmussen L.J. Nuclear localization of human DNA mismatch repair protein exonuclease 1, (hEXO1). Nucl. Acids Res. 2007, 35:2609-2619.
189. Lutzen A., de Wind N., Georgijevic D., Nielsen F., Rasmussen L. Functional analysis of HNPCC-related missense mutations in MSH2. Mutat. Res. 2008, 645:44-55.
190. Belvederesi L., Bianchi F., Galizia E., Loretelli C., Bracci R., Catalani R., Amati M., Cellerino R. MSH2 missense mutations and HNPCC syndrome: pathogenicity assessment in a human expression system. Hum. Mutat. 2008, 29:E296-E309.
191. Kariola R., Raevaara T.E., Lonnqvist K.E., Nystrom-Lahti M. Functional analysis of MSH6 mutations linked to kindreds with putative hereditary non-polyposis colorectal cancer syndrome. Hum. Mol. Genet. 2002, 11:1303-1310.
192. Nystrom-Lahti M., Perrera C., Raschle M., Panyushkina-Seiler E., Marra G., Curci A., Quaresima B., Costanzo F., D'Urso M., Venuta S., Jiricny J. Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer. Genes Chromosomes Cancer 2002, 33:160-167.
193. Ollila S., Dermadi Bebek D., Jiricny J., Nystrom M. Mechanisms of pathogenicity in human MSH2 missense mutants. Hum. Mutat. 2008, 29:1355-1363.
194. Szadkowski M., Iaccarino I., Heinimann K., Marra G., Jiricny J. Characterization of the mismatch repair defect in the human lymphoblastoid MT1 cells. Cancer Res. 2005, 65:4525-4529.
195. Guerrette S., Wilson T., Gradia S., Fishel R. Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer. Mol. Cell Biol. 1998, 18:6616-6623.
196. Guerrette S., Acharya S., Fishel R. The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer. J. Biol. Chem. 1999, 274:6336-6341.
197. Cyr J.L., Heinen C.D. Hereditary cancer-associated missense mutations in hMSH6 uncouple ATP hydrolysis from DNA mismatch binding. J. Biol. Chem. 2008, 283:31641-31648.
198. Heinen C.D., Wilson T., Mazurek A., Berardini M., Butz C., Fishel R. HNPCC mutations in hMSH2 result in reduced hMSH2-hMSH6 molecular switch functions. Cancer Cell 2002, 1:469-478.
199. Li G. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008, 18:85-98.
200. Haber L., Walker G. Altering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities. EMBO J. 1991, 10:2707-2715.
201. Fishel R. Mismatch repair, molecular switches, and signal transduction. Genes Dev. 1998, 12:2096-2101.
202. Sharp A., Pichert G., Lucassen A., Eccles D. RNA analysis reveals splicing mutations and loss of expression defects in MLH1 and BRCA1. Hum. Mutat. 2004, 24:272.
203. Pagenstecher C., Wehner M., Friedl W., Rahner N., Aretz S., Friedrichs N., Sengteller M., Henn W., Buettner R., Propping P., Mangold E. Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. Hum. Genet. 2006, 119:9-22.
204. Auclair J., Busine M., Navarro C., Ruano E., Montmain G., Desseigne F., Saurin J., Lasset C., Bonadona V., Giraud S., Puisieux A., Wang Q. Systematic mRNA analysis for the effect of MLH1 and MSH2 missense and silent mutations on aberrant splicing. Hum. Mutat. 2006, 27:145-154.
205. Woods M.O., Williams P., Careen A., Edwards L., Bartlett S., McLaughlin J.R., Younghusband H.B. A new variant database for mismatch repair genes associated with Lynch syndrome. Hum. Mutat. 2007, 28:669-673.
206. Ou J., Niessen R., Vonk J., Westers H., Hofstra R., Sijmons R. A database to support the interpretation of human mismatch repair gene variants. Hum. Mutat. 2008, 29:1337-1341.
207. Ou J., Niessen R., Lützen A., Sijmons R., Kleibeuker J., de Wind N., Rasmussen L., Hofstra R. Functional analysis helps to clarify the clinical importance of unclassified variants in DNA mismatch repair genes. Hum. Mutat. 2007, 28:1047-1054.
208. Couch F., Rasmussen L., Hofstra R., Monteiro A., Greenblatt M., de Wind N. Assessment of functional effects of unclassified genetic variants. Hum. Mutat. 2008, 29:1314-1326. for the IARC Unclassified Genetic Variants Working Group.
209. Chao E., Velasquez J., Witherspoon M., Rozek L., Peel D., Ng P., Gruber S., Watson P., Rennert G., Anton-Culver H., Lynch H., Lipkin S. Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair, (MAPP-MMR). Hum. Mutat. 2008, 29:852-860.