title: Epigenetic regulation of colon cancer and intestinal stem cells.
abstract: The importance and role of the cellular epigenome in cell fating and development have been studied for decades. The epigenome encompasses a range of attributes including DNA methylation, histone modifications, and chromatin remodelers; together these components define the cellular transcriptome, identity, and function. The cellular epigenome is dynamic in response to environmental signals, modifiable during normal cell differentiation and is heritable in daughter cells. This plasticity, however, poses a risk for misregulation and may underlie a number of hereditary disorders, development defects, and cancer. Although the first epigenetic change described in cancer was gene hypomethylation [Holliday R, Jeggo PA: Mechanisms for changing gene expression and their possible relationship to carcinogenesis.Cancer Surv 1985, 4:557-581; Feinberg AP, Vogelstein B: Hypomethylation distinguishes genes of some human cancers from their normal counterparts.Nature 1983, 301:89-92], we know that cancers not only display global hypomethylation, but also, site-specific gene hypermethylation in addition to changes in chromatin modifications. Mechanisms explaining the sometimes paradoxical epigenetic changes observed in cancer, their contributions to tumor initiation and progression and how epigenetics relate to genetic events are poorly understood. In this review we will briefly discuss recent findings on the epigenomic states observed in colon cancer, in particular, how perturbations to the genome and epigenome together may contribute to initiation and progression of colon cancer.
authors: Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors: Saher Sue
authors: SS
authors: Hammoud
authors: Bradley R
authors: BR
authors: Cairns
authors: David A
authors: DA
authors: Jones
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D057890:Epigenomics; D017491:Genes, APC; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000166:cytology / Q000473:pathology; D009857:Oncogenes; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology
references: Cell. 1996 Oct 18;87(2):159-70
references: 8861899
references: Gastroenterology. 2006 Oct;131(4):1096-109
references: 17030180
references: Cancer Surv. 1985;4(3):557-81
references: 3916656
references: Nat Genet. 2007 Feb;39(2):237-42
references: 17211412
references: Mech Dev. 2001 Mar;101(1-2):3-9
references: 11231054
references: Oncogene. 2006 Dec 4;25(57):7531-7
references: 17143297
references: Cell. 2009 May 15;137(4):623-34
references: 19450512
references: Nat Genet. 1994 Aug;7(4):536-40
references: 7951326
references: Nat Genet. 2005 Apr;37(4):391-400
references: 15765097
references: Clin Exp Metastasis. 1998 Jul;16(5):471-9
references: 10091942
references: Science. 1992 May 1;256(5057):668-70
references: 1350108
references: BMC Med Genomics. 2012 Aug 28;5:38
references: 22929163
references: Cell. 2009 Mar 6;136(5):903-12
references: 19269367
references: Nature. 2011 Jul 04;476(7360):293-7
references: 21727895
references: Nature. 2002 Apr 4;416(6880):552-6
references: 11932749
references: Biochim Biophys Acta. 2003 Jun 5;1653(1):1-24
references: 12781368
references: Trends Microbiol. 2004 Aug;12(8):394-8
references: 15276616
references: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8681-6
references: 10411935
references: Cell. 2000 Oct 13;103(2):311-20
references: 11057903
references: Cancer Res. 1991 Nov 15;51(22):6094-7
references: 1933872
references: Princess Takamatsu Symp. 1991;22:285-92
references: 1668888
references: Cell. 2012 Jun 8;149(6):1245-56
references: 22682247
references: Am J Clin Pathol. 2003 Sep;120(3):418-23
references: 14502807
references: Nat Genet. 2009 Feb;41(2):178-186
references: 19151715
references: J Histochem Cytochem. 1956 Nov;4(6):531-40
references: 13385475
references: Cancer Cell. 2007 Nov;12(5):419-31
references: 17996646
references: Nature. 2009 Jan 29;457(7229):608-11
references: 19092804
references: Genome Res. 2002 Apr;12(4):543-54
references: 11932239
references: Cell. 1991 Aug 9;66(3):589-600
references: 1651174
references: Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):466-71
references: 22190486
references: Cancer Res. 1994 Nov 1;54(21):5523-6
references: 7923189
references: Cancer Res. 2007 Sep 15;67(18):8565-73
references: 17875695
references: Cancer Res. 1994 Nov 1;54(21):5527-30
references: 7923190
references: Oncogene. 2007 Aug 16;26(38):5680-91
references: 17353908
references: Nature. 2002 Oct 10;419(6907):624-9
references: 12374981
references: J Biol Chem. 2004 Dec 3;279(49):51581-9
references: 15358764
references: Nat Genet. 2009 Dec;41(12):1350-3
references: 19881528
references: Nature. 1983 Jan 6;301(5895):89-92
references: 6185846
references: Genome Res. 2012 Feb;22(2):271-82
references: 21659424
references: Nat Genet. 2003 Jan;33(1):61-5
references: 12496760
references: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4036-41
references: 17360473
references: Cancer Res. 1997 Mar 1;57(5):808-11
references: 9041175
references: Nat Genet. 2008 Jul;40(7):915-20
references: 18536716
references: Nat Genet. 2007 Feb;39(2):232-6
references: 17200670
references: EMBO J. 2012 Jun 12;31(14):3079-91
references: 22692129
references: Biochem Biophys Res Commun. 1983 Feb 28;111(1):47-54
references: 6187346
references: Cell. 2010 Sep 17;142(6):930-42
references: 20850014
references: Nature. 2009 Nov 19;462(7271):315-22
references: 19829295
references: PLoS Genet. 2008 Aug 22;4(8):e1000162
references: 18725933
references: Nat Genet. 2008 May;40(5):600-8
references: 18372904
references: J Natl Cancer Inst. 1993 Dec 15;85(24):2004-7
references: 8246286
references: Front Biosci. 1999 Mar 15;4:D286-98
references: 10077541
references: Nature. 1987 Aug 13-19;328(6131):614-6
references: 3039373
references: Science. 1990 Aug 24;249(4971):912-5
references: 2144057
references: Semin Cancer Biol. 2011 Dec;21(6):360-6
references: 21946622
references: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14122-7
references: 16959882
references: Science. 2012 Aug 10;337(6095):730-5
references: 22855427
references: Science. 2003 Apr 18;300(5618):455
references: 12702868
references: Cell. 1991 Aug 9;66(3):601-13
references: 1678319
references: Biochem Biophys Res Commun. 2003 Jul 18;307(1):52-63
references: 12849980
references: Am J Pathol. 2009 Mar;174(3):715-21
references: 19197002
references: Cell Cycle. 2009 Aug 15;8(16):2549-56
references: 19597346
references: Cancer Res. 2010 Feb 15;70(4):1398-407
references: 20145141
references: Nat Genet. 2011 Nov 27;44(1):40-6
references: 22120008
references: Crit Rev Oncog. 2006 Dec;12(3-4):273-87
references: 17425506
references: Nature. 2007 Oct 25;449(7165):1003-7
references: 17934449
references: Science. 1985 Apr 12;228(4696):187-90
references: 2579435
references: J Biol Chem. 2004 Aug 13;279(33):34397-405
references: 15190067
references: Cancer Res. 1994 Nov 15;54(22):5953-8
references: 7954428
references: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7149-53
references: 8692960
references: Nat Genet. 2007 Feb;39(2):157-8
references: 17200673
references: Nature. 2012 Jul 18;487(7407):330-7
references: 22810696
references: J Biol Chem. 2006 Dec 8;281(49):37828-35
references: 17028196
references: Biochem Soc Trans. 2005 Aug;33(Pt 4):672-5
references: 16042571
references: Cancer Res. 1994 Nov 15;54(22):5947-52
references: 7954427
references: Tohoku J Exp Med. 1992 Oct;168(2):141-7
references: 1339098
references: Int J Colorectal Dis. 2004 Mar;19(2):95-101
references: 14534800
references: Genes Chromosomes Cancer. 2002 Oct;35(2):156-63
references: 12203779
references: Gastroenterology. 2009 Jun;136(7):2187-2194.e1
references: 19324043
references: Bioessays. 1999 Dec;21(12):1021-30
references: 10580987
references: Cancer Res. 1995 Oct 15;55(20):4531-5
references: 7553622
references: Hum Genet. 1989 Sep;83(2):155-8
references: 2550354
references: Nat Genet. 2011 Jun 26;43(8):768-75
references: 21706001
references: Int J Exp Pathol. 2000 Apr;81(2):117-43
references: 10762441
references: J Clin Invest. 2000 Jun;105(11):1493-9
references: 10841502
references: Oncogene. 2009 Feb 12;28(6):843-53
references: 19079346
references: Nucleic Acids Res. 1983 Oct 11;11(19):6883-94
references: 6314264
references: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8683-8
references: 12072559
references: Cell. 2008 Dec 26;135(7):1201-12
references: 19109892
references: Cancer Res. 1988 Mar 1;48(5):1159-61
references: 3342396