Saramaki Outi, Visakorpi Tapio
Cancer Genetics, Institute of Medical Technology, University of Tampere, and Tampere University Hospital, Tampere, Finland.
Front Biosci. 2007 May 1;12:3287-301. doi: 10.2741/2312.
Prostate cancer incidence is steadily increasing in Western industrialized countries where it has become the most common male malignancy and second most common cause of cancer death among men. Despite efforts to understand the mechanisms of prostate cancer development and progression, the reasons for the disease remain unclear. Although recurrent DNA copy number aberrations in prostate cancer have been well documented in the past 15 years, most of the target genes for these aberrations remain to be identified. The most common DNA copy number aberrations are losses in chromosomes 5q, 6q, 8p, 10q, 13q, 16q, 17p, and 18q, and gains in 7p/q, 8q, 9p, and Xq. In addition, a chromosomal rearrangement in 21q has been observed in over 50% of prostate cancers. The target genes for two common chromosomal aberrations have been identified: the androgen receptor (AR) gene at Xq12, and TMPRSS2 and ERG at 21q. Putative target genes for other copy number aberrations include: NKX3-1 (8p loss), PTEN and MXI1 (10q loss), FOXO1A (13q loss), CDH1 and ATBF1 (16q loss), MCM7 and EZH2 (7q gain), TCEB1, EIF3S3 and MYC (8q gain). The identification of target genes for the chromosomal aberrations will provide new prognostic markers and therapeutic targets for future drug development.
在西方工业化国家，前列腺癌的发病率正在稳步上升，在这些国家，它已成为最常见的男性恶性肿瘤，也是男性癌症死亡的第二大常见原因。尽管人们努力了解前列腺癌发生和发展的机制，但该疾病的病因仍不清楚。虽然在过去15年中，前列腺癌中反复出现的DNA拷贝数异常已有充分记录，但这些异常的大多数靶基因仍有待确定。最常见的DNA拷贝数异常是5号染色体长臂、6号染色体长臂、8号染色体短臂、10号染色体长臂、13号染色体长臂、16号染色体长臂、17号染色体短臂和18号染色体短臂的缺失，以及7号染色体短臂/长臂、8号染色体长臂、9号染色体短臂和X染色体长臂的增加。此外，在超过50%的前列腺癌中观察到21号染色体的染色体重排。已确定了两种常见染色体异常的靶基因：位于Xq12的雄激素受体（AR）基因，以及位于21号染色体长臂的TMPRSS2和ERG。其他拷贝数异常的推定靶基因包括：NKX3-1（8号染色体短臂缺失）、PTEN和MXI1（10号染色体长臂缺失）、FOXO1A（13号染色体长臂缺失）、CDH1和ATBF1（16号染色体长臂缺失）、MCM7和EZH2（7号染色体长臂增加）、TCEB1、EIF3S3和MYC（8号染色体长臂增加）。确定染色体异常的靶基因为未来药物开发提供新的预后标志物和治疗靶点。
