Role of epigenomics in ovarian and endometrial cancers

被引：36

作者：

Balch, Curtis ^{[1
,2
]}

Matei, Daniela E. ^{[2
,3
,4
]}

Huang, Tim H-M ^{[5
]}

Nephew, Kenneth P. ^{[1
,2
,4
,6
]}

机构：

[1] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Mol Sci Program, Bloomington, IN 47408 USA

[2] Indiana Univ, Melvin & Bren Simon Cancer Ctr, Indianapolis, IN 46202 USA

[3] Indiana Univ Sch Med, Div Hematol Oncol, Dept Med, Indianapolis, IN 46202 USA

[4] Indiana Univ Sch Med, Dept Obstet & Gynecol, Dept Med, Indianapolis, IN 46202 USA

[5] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

[6] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA

来源：

EPIGENOMICS | 2010年 / 2卷 / 03期

关键词：

decitabine; DNA methylation; endometrial cancer; epigenetic biomarker; HDAC inhibitor; histone deacetylase; histone methylation; microRNA; ovarian cancer; HISTONE DEACETYLASE INHIBITORS; TUMOR-SUPPRESSOR GENES; ABERRANT PROMOTER METHYLATION; PLATINUM-BASED CHEMOTHERAPY; PROGRESSION-FREE SURVIVAL; DNA METHYLTRANSFERASE 1; TISSUE-GROWTH-FACTOR; CELL-CYCLE ARREST; EPITHELIAL OVARIAN; DOWN-REGULATION;

D O I：

10.2217/EPI.10.19

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Ovarian cancer is the most lethal gynecologic malignancy and while constituting only 3% of all female cancers, it causes 14,600 deaths in the USA annually. Endometrial cancer, the most diagnosed and second-most fatal gynecologic cancer, afflicts over 40,000 US women annually, causing an estimated 7780 deaths in 2009. In both advanced ovarian and endometrial carcinomas, the majority of initially therapy-responsive tumors eventually evolve to a fully drug-resistant phenotype. In addition to genetic mutations, epigenetic anomalies are frequent in both gynecologic malignancies, including aberrant DNA methylation, atypical histone modifications and dysregulated expression of distinct microRNAs, resulting in altered gene-expression patterns favoring cell survival. In this article, we summarize the most recent hypotheses regarding the role of epigenetics in ovarian and endometrial cancers, including a possible role in tumor 'stemness' and also evaluate the possible therapeutic benefits of reversal of these oncogenic chromatin aberrations.

引用

页码：419 / 447

页数：29

共 295 条

[1] Dominant-negative histone H3 lysine 27 mutant derepresses silenced tumor suppressor genes and reverses the drug-resistant phenotype in cancer cells [J].