Genomic and epigenetic instability in colorectal cancer pathogenesis.
Colorectal cancer arises as a consequence of the accumulation of genetic alterations (gene mutations, gene amplification, and so on) and epigenetic alterations (aberrant DNA methylation, chromatin modifications, and so on) that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic stability and resulting gene alterations are key molecular pathogenic steps that occur early in tumorigenesis; they permit the acquisition of a sufficient number of alterations in tumor suppressor genes and oncogenes that transform cells and promote tumor progression. Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and chromosome instability. Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more effective prevention strategies and therapeutics for patients with colorectal cancer.
Grady
William M
WM
Department of Medicine, University of Washington Medical School, Seattle, Washington, USA.
Carethers
John M
JM
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics; D023281:Genomics; D006801:Humans
J Biol Chem. 2000 Jun 16;275(24):18424-31
10747992
Genes Dev. 2001 Mar 15;15(6):724-36
11274057
Nat Genet. 1999 Oct;23(2):142-4
10508506
Lancet. 2003 Jul 5;362(9377):39-41
12853198
Nature. 1996 Aug 8;382(6591):499-500
8700220
Cancer Cell. 2002 May;1(4):299-305
12086841
J Clin Invest. 1996 Jul 1;98(1):199-206
8690794
Semin Cancer Biol. 2005 Feb;15(1):33-42
15613286
Nat Rev Cancer. 2003 Sep;3(9):701-8
12951589
Am J Pathol. 2001 Sep;159(3):1129-35
11549606
Cancer Res. 1998 Nov 15;58(22):5248-57
9823339
Science. 2002 Sep 20;297(5589):2013
12242432
Annu Rev Genet. 2002;36:617-56
12429704
Science. 1995 Jun 30;268(5219):1912-4
7604265
J Biol Chem. 1997 Apr 18;272(16):10917-21
9099749
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5
9618505
Mol Diagn. 1999 Jun;4(2):153-7
10462630
J Biol Chem. 1998 Jul 31;273(31):19895-901
9677427
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):303-8
10618413
J Clin Oncol. 2006 Aug 10;24(23):3799-808
16896009
Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):11-27
15000146
Biochim Biophys Acta. 2002 Mar 14;1602(1):73-87
11960696
Cancer Res. 1998 Nov 1;58(21):4811-6
9809983
J Clin Oncol. 2005 Jan 20;23(3):609-18
15659508
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4562-7
11904375
Science. 1995 Jun 2;268(5215):1336-8
7761852
Trends Cell Biol. 2001 Jan;11(1):18-21
11146294
Am J Pathol. 2002 May;160(5):1823-30
12000733
Cancer Res. 1995 Dec 1;55(23):5548-50
7585632
Oncogene. 1997 May 8;14(18):2195-200
9174055
Semin Cancer Biol. 2005 Dec;15(6):484-93
16055342
Science. 2001 Aug 10;293(5532):1074-80
11498575
Gastroenterology. 2004 Dec;127(6):1678-84
15578504
Nat Rev Cancer. 2001 Nov;1(2):109-17
11905802
Cancer Cell. 2003 Dec;4(6):483-97
14706340
Cell. 2006 Jul 28;126(2):297-308
16873062
Science. 1995 Jun 30;268(5219):1909-12
7604264
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3925-30
17360454
Science. 1997 Feb 14;275(5302):967-9
9020077
Mol Cell Biol. 2005 May;25(10):4046-61
15870277
Science. 1993 May 7;260(5109):816-9
8484122
N Engl J Med. 2003 Feb 27;348(9):791-9
12606733
Genes Dev. 2004 Jun 1;18(11):1331-44
15175264
Cancer Res. 1996 Nov 1;56(21):4881-6
8895738
Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R159-65
12915454
Cancer Cell. 2007 Jan;11(1):25-36
17189716
Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8681-6
10411935
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8698-702
9671741
Nat Genet. 1999 Feb;21(2):163-7
9988266
Curr Biol. 1996 Sep 1;6(9):1181-4
8805365
Science. 1994 Dec 23;266(5193):2011-5
7605428
Hum Mol Genet. 1998;7(10):1555-63
9735376
Trends Genet. 2000 Apr;16(4):168-74
10729832
Cancer Genet Cytogenet. 2001 Apr 1;126(1):13-9
11343773
Annu Rev Biochem. 2005;74:681-710
15952900
J Pathol. 2001 Sep;195(1):111-34
11568897
Nat Rev Cancer. 2006 Jul;6(7):493-505
16794633
Cancer Res. 1982 Aug;42(8):3005-9
6212116
FEBS Lett. 1992 Sep 7;309(2):193-8
1324197
J Biol Chem. 2000 Nov 24;275(47):36498-501
11005803
Gut. 2008 Jul;57(7):941-50
18364437
Nature. 1994 Mar 17;368(6468):258-61
8145827
Gastroenterology. 1999 Jul;117(1):123-31
10381918
Cancer Biol Ther. 2006 Jul;5(7):714-20
16861898
Cancer Res. 1995 Sep 1;55(17):3721-5
7641183
Int J Cancer. 2003 Aug 10;106(1):66-73
12794758
Cancer Res. 2004 May 15;64(10):3391-4
15150090
Lancet. 2000 Feb 26;355(9205):716-9
10703804
Genomics. 2008 Jun;91(6):508-11
18434084
Cancer Res. 2003 Jul 1;63(13):3511-6
12839935
Nature. 1997 Apr 10;386(6625):623-7
9121588
Nature. 2000 Aug 10;406(6796):641-5
10949306
Nat Genet. 2000 Nov;26(3):375-8
11062484
Hum Mol Genet. 2001 Dec 15;10(26):3001-7
11751682
Nat Rev Cancer. 2004 Mar;4(3):197-205
14993901
Semin Cancer Biol. 2005 Feb;15(1):43-9
15613287
Gastroenterology. 2008 Apr;134(4):988-97
18395080
Lancet Oncol. 2004 Oct;5(10):600-6
15465463
N Engl J Med. 2001 Apr 19;344(16):1196-206
11309634
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8412-7
12829793
Oncogene. 1998 Aug 13;17(6):719-25
9715273
Gastroenterology. 2005 Sep;129(3):837-45
16143123
Gastroenterol Clin North Am. 1996 Dec;25(4):755-72
8960891
Nat Rev Genet. 2008 Mar;9(3):204-17
18227811
Nature. 1998 Jun 4;393(6684):487-91
9624007
Nat Genet. 2003 Feb;33(2):197-202
12539045
Genes Chromosomes Cancer. 1995 Feb;12(2):97-109
7535093
Gastroenterology. 2004 Feb;126(2):394-401
14762775
Science. 1994 Mar 18;263(5153):1625-9
8128251
Nature. 2005 Apr 14;434(7035):864-70
15829956
Gut. 2006 Jun;55(6):848-55
16299036
Nat Rev Cancer. 2007 Dec;7(12):911-24
18004399
Cancer Cell. 2003 Aug;4(2):121-31
12957287
Science. 2002 Jul 26;297(5581):547-51
12142523
Cell. 1995 Apr 7;81(1):95-105
7720077
Chromosoma. 2001 May;110(2):65-74
11453556
Science. 2001 Nov 9;294(5545):1343-6
11598267
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16226-31
12446840
BMC Genet. 2006 Jan 17;7:3
16417627
Cancer Cell. 2002 Aug;2(2):149-55
12204535
Cell. 1993 Dec 17;75(6):1215-25
8261515
Cancer Res. 1998 Jul 15;58(14):3101-4
9679977
Nat Rev Genet. 2005 Aug;6(8):611-22
16136653
Cell. 1990 Jun 1;61(5):759-67
2188735
Science. 2002 Jul 26;297(5581):565-9
12142527
Mol Cell Biol. 1994 Jul;14(7):4731-40
8007975
Mol Cell Biol. 2002 Apr;22(7):2037-46
11884592
Oncogene. 2001 Oct 25;20(48):7120-7
11704838
Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):29-39
15000147
Cancer Res. 1997 Mar 1;57(5):808-11
9041175
Cancer Res. 2004 May 1;64(9):2998-3001
15126332
Cancer Cell. 2005 Jul;8(1):35-47
16023597
Mol Cell. 2004 Apr 9;14(1):105-16
15068807
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12384-8
10535931
Cell. 1998 Apr 3;93(1):81-91
9546394
Science. 1995 Jun 30;268(5219):1915-7
7604266
Gastroenterology. 2007 Feb;132(2):633-44
17258738
Dev Cell. 2001 Aug;1(2):227-37
11702782
Mol Cell. 2004 Jul 2;15(1):31-41
15225546
Front Biosci. 2008 Jan 01;13:2103-14
17981695
Genes Dev. 1999 Jan 15;13(2):152-7
9925639
Annu Rev Biochem. 1996;65:101-33
8811176
Oncogene. 2002 Sep 9;21(40):6146-53
12214243
Cancer Res. 2001 Mar 1;61(5):2212-9
11280789
Am J Pathol. 2003 May;162(5):1545-8
12707038
Nature. 2004 Mar 4;428(6978):77-81
14999283
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1978-83
11830638
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15121-6
10611348
Gastroenterology. 1998 Feb;114(2):268-74
9453486
Curr Opin Genet Dev. 1999 Feb;9(1):69-75
10072359
Oncogene. 1999 Sep 23;18(39):5473-6
10498901
Cell. 1997 Dec 26;91(7):995-1005
9428522
Cancer Res. 1999 Oct 15;59(20):5068-74
10537275
Nat Genet. 2002 Feb;30(2):227-32
11818965
Cancer Res. 2005 Aug 1;65(15):6488-92
16061623
Cancer Res. 1995 Oct 15;55(20):4525-30
7553621
EMBO J. 2002 Nov 1;21(21):5911-20
12411508
J Biol Chem. 2005 Feb 18;280(7):5516-26
15611052
Nat Genet. 2004 Jan;36(1):63-8
14702042
Cell. 2001 May 18;105(4):445-57
11371342
Cancer Res. 1997 Oct 1;57(19):4420-6
9331106
N Engl J Med. 2003 Jul 17;349(3):247-57
12867608
Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1236-41
10655514
Cancer Res. 1998 Oct 15;58(20):4537-42
9788596
Proc Natl Acad Sci U S A. 1985 Nov;82(21):7350-4
2997788
Nature. 1998 Dec 17;396(6712):643-9
9872311
Cancer Res. 1999 May 15;59(10):2307-12
10344734
Gastroenterology. 2004 Mar;126(3):654-9
14988818
Int J Cancer. 2004 Apr 10;109(3):468-71
14961589
Cancer Res. 2005 Jun 1;65(11):4683-9
15930286
J Biol Chem. 1991 Feb 25;266(6):3744-51
1995629
Nature. 1998 Mar 19;392(6673):300-3
9521327
J Natl Cancer Inst. 2004 Jan 7;96(1):68-70
14709740
Science. 2002 Jul 26;297(5581):552-7
12142524
Nature. 1998 Aug 13;394(6694):616-7
9716124
Cancer Res. 1994 Nov 1;54(21):5539-42
7923193
J Biol Chem. 1999 Mar 12;274(11):7474-81
10066813
Annu Rev Genomics Hum Genet. 2002;3:101-28
12142355
Fam Cancer. 2008;7(1):41-52
17636426
Nat Cell Biol. 2001 Apr;3(4):433-8
11283620
Cancer Res. 2006 Mar 1;66(5):2514-9
16510566
Oncogene. 1998 Oct 29;17(17):2187-93
9811450
Cancer J. 2001 Jan-Feb;7(1):40-51
11269647
Nat Genet. 1994 Dec;8(4):405-10
7894494
Cell. 2000 Jan 7;100(1):57-70
10647931
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16910-5
12486240
N Engl J Med. 2000 Jan 13;342(2):69-77
10631274
Nature. 2007 Aug 2;448(7153):595-9
17671502
Nature. 2006 Oct 5;443(7111):541-7
17024086
Nature. 1994 Sep 1;371(6492):75-80
8072530
Nature. 2004 Nov 18;432(7015):338-41
15549096
Nat Genet. 1998 Oct;20(2):104-6
9771694
Clin Cancer Res. 2005 Feb 1;11(3):1203-9
15709190
Cancer Res. 1997 Sep 15;57(18):3920-3
9307272
Cancer Res. 2001 Aug 15;61(16):6046-9
11507051
Int J Cancer. 2006 May 15;118(10):2509-13
16380996
Cell Cycle. 2005 Oct;4(10):1377-81
16205112
Mol Cell. 1999 Feb;3(2):255-61
10078208
Nat Genet. 1998 Oct;20(2):189-93
9771714
J Biol Chem. 2006 Aug 4;281(31):21607-21616
16731533
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3940-4
10097142
Nature. 2001 Jan 18;409(6818):355-9
11201745
Gut. 2007 Nov;56(11):1564-71
17339237
Nat Rev Cancer. 2003 Sep;3(9):695-701
12951588
Cancer Res. 1996 Aug 15;56(16):3645-50
8706000
Gastroenterology. 2004 Jan;126(1):42-8
14699485
Genes Dev. 1998 Jul 15;12(14):2096-101
9679053
Cancer Res. 1994 Apr 1;54(7):1645-8
8137274
Mol Cell. 2003 Nov;12(5):1077-86
14636568
Cancer Res. 1999 May 1;59(9):2023-8
10232579
Cell. 1993 Dec 3;75(5):1027-38
8252616
EMBO J. 1998 Jun 1;17(11):3052-65
9606188
Clin Cancer Res. 2003 Nov 15;9(15):5607-15
14654542
Oncogene. 2005 Jun 9;24(25):4017-25
15806166
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):191-5
14734469
Med Hypotheses. 2002 Dec;59(6):667-9
12445507
Nature. 1993 Jun 10;363(6429):558-61
8505985
Nat Genet. 1998 May;19(1):39-46
9590286
Nature. 2001 Jun 28;411(6841):1073-6
11429610
Cancer Res. 2001 Feb 1;61(3):818-22
11221861
J Biol Chem. 2003 Feb 7;278(6):3891-6
12458199
Nat Genet. 1996 Nov;14(3):255-7
8896552
Science. 1996 Oct 11;274(5285):246-8
8824189
Cell. 2005 Sep 9;122(5):693-705
16143102
Nat Genet. 2006 Jul;38(7):787-93
16804544
Gastroenterol Clin North Am. 1996 Dec;25(4):737-54
8960890
Nat Genet. 2001 Jun;28(2):155-9
11381263
Science. 1993 May 7;260(5109):812-6
8484121
Science. 2007 Nov 16;318(5853):1108-13
17932254
Cell. 1996 Oct 4;87(1):65-73
8858149
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18654-9
18003927
Nature. 2005 Jun 30;435(7046):1262-6
15988529
Ann Surg Oncol. 2001 Oct;8(9):729-40
11597015
J Biol Chem. 2004 May 14;279(20):20935-40
15014079
Cell. 1998 Feb 20;92(4):433-6
9491884