title: The causes and consequences of genetic heterogeneity in cancer evolution.
abstract: Recent studies have revealed extensive genetic diversity both between and within tumours. This heterogeneity affects key cancer pathways, driving phenotypic variation, and poses a significant challenge to personalized cancer medicine. A major cause of genetic heterogeneity in cancer is genomic instability. This instability leads to an increased mutation rate and can shape the evolution of the cancer genome through a plethora of mechanisms. By understanding these mechanisms we can gain insight into the common pathways of tumour evolution that could support the development of future therapeutic strategies.
authors.affiliation: Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Burrell
authors.forename: Nicholas
authors.initials: N
authors.lastname: McGranahan
authors.forename: Jiri
authors.initials: J
authors.lastname: Bartek
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D000818:Animals; D018450:Disease Progression; D018740:Genetic Heterogeneity; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
references.citation: Curr Biol. 2009 Dec 1;19(22):1937-42
references.pmid: 19879145
references.citation: Cancer Res. 2006 Apr 15;66(8):3987-91
references.pmid: 16618716
references.citation: Nature. 2013 Feb 28;494(7438):492-496
references.pmid: 23446422
references.citation: Nature. 2010 Oct 28;467(7319):1109-13
references.pmid: 20981101
references.citation: J Clin Oncol. 2012 Aug 20;30(24):2956-62
references.pmid: 22665543
references.citation: Nature. 2012 May 16;486(7403):400-4
references.pmid: 22722201
references.citation: Mol Cell. 2012 Mar 30;45(6):710-8
references.pmid: 22464441
references.citation: Nature. 2013 Jul 11;499(7457):214-218
references.pmid: 23770567
references.citation: Science. 2011 Aug 19;333(6045):1039-43
references.pmid: 21852505
references.citation: Bioessays. 1993 Jul;15(7):477-84
references.pmid: 7691058
references.citation: Nature. 2012 Jan 18;481(7381):287-94
references.pmid: 22258607
references.citation: Cancer Cell. 2011 Dec 13;20(6):810-7
references.pmid: 22137795
references.citation: Cell. 2012 Sep 14;150(6):1121-34
references.pmid: 22980976
references.citation: J Pathol. 2012 Apr;226(5):703-12
references.pmid: 22183581
references.citation: Nat Genet. 2013 Feb;45(2):136-44
references.pmid: 23263490
references.citation: Oncologist. 2012;17(7):978-85
references.pmid: 22673630
references.citation: Nat Cell Biol. 2009 Jan;11(1):27-35
references.pmid: 19060894
references.citation: Cancer Res. 2012 Dec 1;72(23):6279-89
references.pmid: 23204322
references.citation: Nat Rev Cancer. 2006 Dec;6(12):924-35
references.pmid: 17109012
references.citation: Science. 1995 Jun 2;268(5215):1336-8
references.pmid: 7761852
references.citation: Nature. 2012 Feb 15;482(7386):529-33
references.pmid: 22343890
references.citation: J Clin Oncol. 2005 Jan 20;23(3):609-18
references.pmid: 15659508
references.citation: Nat Rev Genet. 2012 Nov;13(11):795-806
references.pmid: 23044827
references.citation: Nature. 2010 Mar 18;464(7287):436-40
references.pmid: 20173739
references.citation: Genes Dev. 2010 Aug 15;24(16):1731-45
references.pmid: 20713517
references.citation: Nat Biotechnol. 2012 May;30(5):413-21
references.pmid: 22544022
references.citation: Cancer Res. 2012 Oct 1;72(19):4875-82
references.pmid: 23002210
references.citation: Cancer Res. 2011 May 15;71(10):3447-52
references.pmid: 21270108
references.citation: Science. 2013 Feb 1;339(6119):543-8
references.pmid: 23239622
references.citation: Semin Cancer Biol. 2010 Oct;20(5):279-80
references.pmid: 20937389
references.citation: Science. 2011 Mar 4;331(6021):1199-203
references.pmid: 21252315
references.citation: Nat Rev Cancer. 2010 Nov;10(11):760-74
references.pmid: 20966921
references.citation: N Engl J Med. 2003 Feb 27;348(9):791-9
references.pmid: 12606733
references.citation: Cancer Genet Cytogenet. 2010 Apr 1;198(1):47-51
references.pmid: 20303014
references.citation: Nat Rev Clin Oncol. 2009 Dec;6(12):718-30
references.pmid: 19942925
references.citation: Cell. 2012 Jul 20;150(2):264-78
references.pmid: 22817890
references.citation: Cancer Cell. 2007 Jan;11(1):25-36
references.pmid: 17189716
references.citation: Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10529-33
references.pmid: 8248141
references.citation: PLoS One. 2009 Aug 10;4(8):e6564
references.pmid: 19668340
references.citation: Nature. 2009 Jul 9;460(7252):278-82
references.pmid: 19506557
references.citation: EMBO J. 2007 Jul 25;26(14):3397-409
references.pmid: 17599064
references.citation: Nature. 2012 Jun 28;486(7404):537-40
references.pmid: 22722843
references.citation: Nature. 2011 Jan 20;469(7330):356-61
references.pmid: 21160474
references.citation: Science. 2013 Mar 29;339(6127):1546-58
references.pmid: 23539594
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-892
references.pmid: 22397650
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7081-4
references.pmid: 8692948
references.citation: Oncogene. 2002 Oct 21;21(48):7435-51
references.pmid: 12379884
references.citation: Nature. 2012 Jan 26;483(7387):100-3
references.pmid: 22281684
references.citation: Nature. 1997 Apr 10;386(6625):623-7
references.pmid: 9121588
references.citation: N Engl J Med. 2009 Jul 9;361(2):123-34
references.pmid: 19553641
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8699-704
references.pmid: 15159543
references.citation: Nature. 2010 Apr 15;464(7291):999-1005
references.pmid: 20393555
references.citation: Nat Rev Genet. 2012 Jan 24;13(3):189-203
references.pmid: 22269907
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12111-6
references.pmid: 17626182
references.citation: Cancer Res. 2003 Sep 1;63(17):5564-72
references.pmid: 14500396
references.citation: N Engl J Med. 2012 Mar 22;366(12):1079-89
references.pmid: 22417203
references.citation: Nature. 2005 Apr 14;434(7035):864-70
references.pmid: 15829956
references.citation: Cancer Cell. 2009 Dec 8;16(6):475-86
references.pmid: 19962666
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):961-8
references.pmid: 20080596
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3041-6
references.pmid: 22323597
references.citation: Trends Mol Med. 2011 Feb;17(2):88-96
references.pmid: 21087899
references.citation: Nature. 2005 Apr 14;434(7035):913-7
references.pmid: 15829966
references.citation: Annu Rev Genet. 2004;38:615-43
references.pmid: 15568988
references.citation: Biol Open. 2012 Jan 15;1(1):12-8
references.pmid: 23213363
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4009-14
references.pmid: 23412337
references.citation: Cancer Cell. 2008 Aug 12;14(2):111-22
references.pmid: 18656424
references.citation: Cancer Prev Res (Phila). 2010 Nov;3(11):1388-97
references.pmid: 20947487
references.citation: Cell. 2011 Jan 7;144(1):27-40
references.pmid: 21215367
references.citation: JAMA. 2011 Oct 12;306(14):1557-65
references.pmid: 21990299
references.citation: Science. 2011 Sep 30;333(6051):1895-8
references.pmid: 21960636
references.citation: Curr Opin Genet Dev. 2007 Apr;17(2):157-62
references.pmid: 17324569
references.citation: Mol Cell. 2011 Mar 4;41(5):543-53
references.pmid: 21362550
references.citation: EMBO Rep. 2012 Jun 01;13(6):528-38
references.pmid: 22595889
references.citation: Nature. 2010 Feb 18;463(7283):893-8
references.pmid: 20164919
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8644-9
references.pmid: 11447276
references.citation: Science. 1976 Oct 1;194(4260):23-8
references.pmid: 959840
references.citation: Gastroenterology. 2010 Apr;138(4):1441-54, 1454.e1-7
references.pmid: 20102718
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14800-3
references.pmid: 8962135
references.citation: Cell. 2013 Jan 31;152(3):620-32
references.pmid: 23352430
references.citation: Blood. 2012 Aug 2;120(5):1067-76
references.pmid: 22498740
references.citation: Cancer Res. 2011 Mar 1;71(5):1858-70
references.pmid: 21363922
references.citation: Nature. 1998 Mar 19;392(6673):300-3
references.pmid: 9521327
references.citation: Nature. 2011 Apr 7;472(7341):90-4
references.pmid: 21399628
references.citation: Science. 2008 Mar 7;319(5868):1352-5
references.pmid: 18323444
references.citation: Nat Rev Cancer. 2011 Apr;11(4):237-8
references.pmid: 21548400
references.citation: Nat Rev Cancer. 2009 Sep;9(9):665-74
references.pmid: 19693095
references.citation: Cell. 2011 Sep 16;146(6):889-903
references.pmid: 21925314
references.citation: Nature. 2012 Jul 18;487(7407):330-7
references.pmid: 22810696
references.citation: Nature. 2012 Apr 04;486(7403):395-9
references.pmid: 22495314
references.citation: Chromosoma. 2008 Dec;117(6):511-9
references.pmid: 18528701
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Cancer Cell. 2007 Jan;11(1):9-23
references.pmid: 17189715
references.citation: J Pathol. 2012 Aug;227(4):446-55
references.pmid: 22514011
references.citation: Nature. 2001 May 17;411(6835):366-74
references.pmid: 11357144
references.citation: Nat Rev Cancer. 2005 Mar;5(3):231-7
references.pmid: 15738985
references.citation: Nature. 2006 Nov 30;444(7119):633-7
references.pmid: 17136093
references.citation: Nature. 2013 Aug 22;500(7463):415-21
references.pmid: 23945592
references.citation: Mol Oncol. 2011 Aug;5(4):308-14
references.pmid: 21641882
references.citation: Carcinogenesis. 2010 Jan;31(1):9-18
references.pmid: 19887512
references.citation: Front Med. 2012 Sep;6(3):263-74
references.pmid: 22865120
references.citation: J Cell Biol. 2010 Feb 8;188(3):369-81
references.pmid: 20123995
references.citation: Nature. 2012 Jan 18;482(7383):53-8
references.pmid: 22258507
references.citation: Genetics. 2008 Jun;179(2):737-46
references.pmid: 18558649
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4283-8
references.pmid: 18337506
references.citation: Nucleic Acids Res. 2009 Aug;37(14):4603-12
references.pmid: 19494183
references.citation: Nature. 2010 Jan 28;463(7280):545-8
references.pmid: 20072127
references.citation: Nat Struct Mol Biol. 2010 Jun;17(6):688-95
references.pmid: 20453858
references.citation: Nature. 2009 Oct 8;461(7265):809-13
references.pmid: 19812674
references.citation: Nat Rev Cancer. 2012 Apr 19;12(5):323-34
references.pmid: 22513401
references.citation: Cell. 2013 Feb 14;152(4):714-26
references.pmid: 23415222
references.citation: Nat Med. 1995 Dec;1(12):1245-6
references.pmid: 7489399
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2183-94
references.pmid: 21784954
references.citation: Cell. 2012 May 25;149(5):994-1007
references.pmid: 22608083
references.citation: J Pathol. 2013 Aug;230(4):356-64
references.pmid: 23716380
references.citation: Nature. 2010 Jan 21;463(7279):360-3
references.pmid: 20054297
references.citation: Nature. 2010 Oct 28;467(7319):1114-7
references.pmid: 20981102
references.citation: Genes Chromosomes Cancer. 2010 Apr;49(4):368-78
references.pmid: 20088004
references.citation: J Cell Biol. 2008 Feb 25;180(4):665-72
references.pmid: 18283116
references.citation: Cancer Res. 2010 Jan 15;70(2):431-5
references.pmid: 20068152
references.citation: Nature. 2012 Jan 18;481(7381):306-13
references.pmid: 22258609
references.citation: Nature. 2005 Apr 14;434(7035):907-13
references.pmid: 15829965
references.citation: Nature. 2012 Jan 11;481(7382):506-10
references.pmid: 22237025
references.citation: Nature. 1975 May 15;255(5505):197-200
references.pmid: 1143315