Koochekpour S
Department of Urology and Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University, Health Sciences Center, New Orleans, USA.
Iran Red Crescent Med J. 2011 Feb;13(2):80-98. Epub 2011 Feb 1.
Acquired or inherited genetic alterations either alone or in combination with epigenetic alterations are associated with prostate carcinogenesis and its progression toward advance metastatic or castration-resistant disease. A major objective of translational cancer research in post-genome era is to discover the repertoire of genetic and epigenetic variations associated with prostate cancer. Genome-wide association studies have been at least partially successful in identifying potential germline polymorphisms and allelic imbalances such as microsatellite instability and loss of heterozygosity associated with prostate cancer susceptibility. Epigenetic mechanisms such as DNA hyper- or hypomethylation and histone modifications are reversible genetic alterations which allow stable inheritance of cellular phenotypes without any changes in the DNA sequence or quantity. Epigenetic modifications can potentially be used for the molecular classification, detection, and risk assessment in prostate cancer. Chemical inhibitors of DNA methyltransferases and histone deacetylases have been used in different clinical trials and hold promise as novel chemotherapeutics to be effective alone or in combination with other therapeutic interventions in prostate cancer.
获得性或遗传性基因改变单独或与表观遗传改变相结合，与前列腺癌的发生及其向晚期转移性或去势抵抗性疾病的进展相关。后基因组时代转化癌症研究的一个主要目标是发现与前列腺癌相关的基因和表观遗传变异。全基因组关联研究在识别潜在的种系多态性和等位基因失衡（如与前列腺癌易感性相关的微卫星不稳定性和杂合性缺失）方面至少取得了部分成功。DNA高甲基化或低甲基化以及组蛋白修饰等表观遗传机制是可逆的基因改变，可使细胞表型稳定遗传，而DNA序列或数量无任何变化。表观遗传修饰有可能用于前列腺癌的分子分类、检测和风险评估。DNA甲基转移酶和组蛋白脱乙酰酶的化学抑制剂已用于不同的临床试验，并有望作为新型化疗药物单独或与其他治疗干预措施联合用于前列腺癌时发挥疗效。
