The epigenetic progenitor origin of human cancer

被引：1325
作者：
Feinberg, AP
Ohlsson, R
Henikoff, S
机构：
[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[4] Uppsala Univ, Dept Genet & Dev, Uppsala, Sweden
[5] Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98109 USA
来源：
NATURE REVIEWS GENETICS | 2006年 / 7卷 / 01期
关键词：
D O I：
10.1038/nrg1748
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.
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页码：21 / 33
页数：13
相关论文
共 149 条
[1]   Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease [J].
Aaltonen, LA ;
Salovaara, R ;
Kristo, P ;
Canzian, F ;
Hemminki, A ;
Peltomäki, P ;
Chadwick, RB ;
Kääriäinen, H ;
Eskelinen, M ;
Järvinen, H ;
Mecklin, JP ;
de la Chapelle, A ;
Percesepe, A ;
Ahtola, H ;
Härkönen, N ;
Julkunen, R ;
Kangas, E ;
Ojala, S ;
Tulikoura, J ;
ValKamo, E .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (21) :1481-1487
[2]   Cell-type-specific repression of the maspin gene is disrupted frequently by demethylation at the promoter region in gastric intestinal metaplasia and cancer cells [J].
Akiyama, Y ;
Maesawa, C ;
Ogasawara, S ;
Terashima, M ;
Masuda, T .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (05) :1911-1919
[3]   Gli and hedgehog in cancer:: Tumours, embryos and stem cells [J].
Altaba, AR ;
Sánchez, P ;
Dahmane, N .
NATURE REVIEWS CANCER, 2002, 2 (05) :361-372
[4]  
[Anonymous], P NATL ACAD SCI USA
[5]  
[Anonymous], 1986, FUNDAMENTALS ONCOLOG
[6]   Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice [J].
Artandi, SE ;
Chang, S ;
Lee, SL ;
Alson, S ;
Gottlieb, GJ ;
Chin, L ;
DePinho, RA .
NATURE, 2000, 406 (6796) :641-645
[7]   Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes:: Correlation with mutation spectra in vivo [J].
Beale, RCL ;
Petersen-Mahrt, SK ;
Watt, IN ;
Harris, RS ;
Rada, C ;
Neuberger, MS .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 337 (03) :585-596
[8]  
BERENBLUM I, 1962, GEN PATHOLOGY
[9]   DNA methylation patterns and epigenetic memory [J].
Bird, A .
GENES & DEVELOPMENT, 2002, 16 (01) :6-21
[10]   An integrated epigenetic and genetic approach to common human disease [J].
Bjornsson, HT ;
Fallin, MD ;
Feinberg, AP .
TRENDS IN GENETICS, 2004, 20 (08) :350-358
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