Epigenetics in cancer

被引:1943
作者
Sharma, Shikhar [1 ,2 ]
Kelly, Theresa K. [1 ]
Jones, Peter A. [1 ]
机构
[1] Univ So Calif, Dept Urol Biochem & Mol Biol, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90089 USA
[2] Univ So Calif, Dept Genet Mol & Cellular Biol, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90089 USA
关键词
TUMOR-SUPPRESSOR GENES; BINDING PROTEIN MECP2; EMBRYONIC STEM-CELLS; DNA METHYLATION; HISTONE DEACETYLASE; CHROMOSOMAL INSTABILITY; DEVELOPMENTAL GENES; DOWN-REGULATION; TARGET GENES; CPG-ISLANDS;
D O I
10.1093/carcin/bgp220
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. The initiation and progression of cancer, traditionally seen as a genetic disease, is now realized to involve epigenetic abnormalities along with genetic alterations. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer including DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. The reversible nature of epigenetic aberrations has led to the emergence of the promising field of epigenetic therapy, which is already making progress with the recent FDA approval of three epigenetic drugs for cancer treatment. In this review, we discuss the current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies.
引用
收藏
页码:27 / 36
页数:10
相关论文
共 138 条
[1]   GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer [J].
Akiyama, Y ;
Watkins, N ;
Suzuki, H ;
Jair, KW ;
van Engeland, M ;
Esteller, M ;
Sakai, H ;
Ren, CY ;
Yuasa, Y ;
Herman, JG ;
Baylin, SB .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (23) :8429-8439
[2]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[3]   Chromatin signatures of pluripotent cell lines [J].
Azuara, V ;
Perry, P ;
Sauer, S ;
Spivakov, M ;
Jorgensen, HF ;
John, RM ;
Gouti, M ;
Casanova, M ;
Warnes, G ;
Merkenschlager, M ;
Fisher, AG .
NATURE CELL BIOLOGY, 2006, 8 (05) :532-U189
[4]   High-resolution profiling of histone methylations in the human genome [J].
Barski, Artern ;
Cuddapah, Suresh ;
Cui, Kairong ;
Roh, Tae-Young ;
Schones, Dustin E. ;
Wang, Zhibin ;
Wei, Gang ;
Chepelev, Iouri ;
Zhao, Keji .
CELL, 2007, 129 (04) :823-837
[5]   Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? [J].
Baylin, SB ;
Ohm, JE .
NATURE REVIEWS CANCER, 2006, 6 (02) :107-116
[6]   DNA methylation and gene silencing in cancer [J].
Baylin S.B. .
Nature Clinical Practice Oncology, 2005, 2 (Suppl 1) :S4-S11
[7]  
Belinsky SA, 2003, CANCER RES, V63, P7089
[8]   A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].
Bernstein, BE ;
Mikkelsen, TS ;
Xie, XH ;
Kamal, M ;
Huebert, DJ ;
Cuff, J ;
Fry, B ;
Meissner, A ;
Wernig, M ;
Plath, K ;
Jaenisch, R ;
Wagschal, A ;
Feil, R ;
Schreiber, SL ;
Lander, ES .
CELL, 2006, 125 (02) :315-326
[9]   The mammalian epigenome [J].
Bernstein, Bradley E. ;
Meissner, Alexander ;
Lander, Eric S. .
CELL, 2007, 128 (04) :669-681
[10]   DNA methylation patterns and epigenetic memory [J].
Bird, A .
GENES & DEVELOPMENT, 2002, 16 (01) :6-21