Herman J G
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Cold Spring Harb Symp Quant Biol. 2005;70:329-33. doi: 10.1101/sqb.2005.70.036.
Recent studies have identified an increasing number of genes that are inactivated by promoter region methylation in cancer. Some of these genes were initially identified as altered genetically in cancer, but in other tumors they are silenced in association with promoter region CpG island methylation. New approaches for screening the genome add to this list of candidate tumor suppressor genes, and many genes regulated key pathways in cancer, including cell cycle control, DNA repair, and apoptosis. Transcription factors may also be silenced by promoter region methylation, affecting the expression of many downstream target genes and globally altering the cancer phenotype. Determining loss of expression is important in assigning functional importance to promoter region methylation for any gene. Individual cancers have alterations in many different genes, affecting many of these important pathways and contributing to the cancer phenotype. The number of genes targeted for promoter region methylation increases during neoplastic progression. These studies suggest that the epigenetic change of promoter region methylation plays a critical role in neoplastic transformation and progression.
最近的研究发现，越来越多的基因在癌症中因启动子区域甲基化而失活。其中一些基因最初被鉴定为在癌症中发生了基因改变，但在其他肿瘤中，它们与启动子区域CpG岛甲基化相关而沉默。筛选基因组的新方法增加了这一候选肿瘤抑制基因列表，许多基因调控癌症中的关键通路，包括细胞周期控制、DNA修复和细胞凋亡。转录因子也可能因启动子区域甲基化而沉默，影响许多下游靶基因的表达并整体改变癌症表型。确定表达缺失对于确定任何基因启动子区域甲基化的功能重要性很重要。个体癌症在许多不同基因中存在改变，影响许多这些重要通路并促成癌症表型。在肿瘤进展过程中，靶向启动子区域甲基化的基因数量会增加。这些研究表明，启动子区域甲基化的表观遗传变化在肿瘤转化和进展中起关键作用。
