Sun Xiuju, Huang Jian, Homma Taku, Kita Daisuke, Klocker Helmut, Schafer Georg, Boyle Peter, Ohgaki Hiroko
International Agency for Research on Cancer, Lyon, France.
Anticancer Res. 2009 May;29(5):1739-43.
Alterations in the PIK3CA and PTEN genes were assessed in 40 prostate tumors (radical prostatectomy samples). Genetic analyses in glands of the highest Gleason pattern within each tumor revealed PIK3CA amplification in 13%, PIK3CA mutations in 3%, PTEN homozygous deletion in 13% and PTEN hemizygous deletion in 8% of the cases analyzed. Supporting the view that PTEN and PIK3CA act in the same PI3K signaling pathway, genetic alterations in the PIK3CA and PTEN genes were mutually exclusive, except in one tumor. Overall, 13 of the 40 (33%) prostate tumors had alterations in the PI3K pathway. For cases with genetic alterations, other tumor areas with lower Gleason patterns as well as non-tumorous prostate glands were also analyzed. Of nine tumors with Gleason score 7, five cases contained the same genetic alterations in tumor areas of Gleason patterns 3 and 4, whereas in another four cases, genetic alterations were detected only in tumor areas of Gleason 4 but not Gleason 3 patterns. There were no alterations in non-tumorous glands. These results suggest that genetic alterations in the PI3K pathway are common in prostate cancer, and occur mainly through PIK3CA amplification and PTEN hemizygous or homozygous deletion. Glands of Gleason pattern 3 are genetically heterogeneous, some containing the same genetic alterations observed in glands of Gleason pattern 4.
在40例前列腺肿瘤（根治性前列腺切除术样本）中评估了PIK3CA和PTEN基因的改变。对每个肿瘤中Gleason分级最高的腺体进行基因分析，结果显示，在分析的病例中，13%存在PIK3CA扩增，3%存在PIK3CA突变，13%存在PTEN纯合缺失，8%存在PTEN半合子缺失。支持PTEN和PIK3CA在同一PI3K信号通路中起作用这一观点的是，PIK3CA和PTEN基因的基因改变相互排斥，但有一个肿瘤除外。总体而言，40例前列腺肿瘤中有13例（33%）PI3K通路存在改变。对于有基因改变的病例，还分析了其他Gleason分级较低的肿瘤区域以及非肿瘤性前列腺腺体。在9例Gleason评分为7的肿瘤中，5例在Gleason分级为3和4的肿瘤区域存在相同的基因改变，而在另外4例中，仅在Gleason分级为4的肿瘤区域检测到基因改变，而在Gleason分级为3的区域未检测到。非肿瘤性腺体未发现改变。这些结果表明，PI3K通路的基因改变在前列腺癌中很常见，主要通过PIK3CA扩增以及PTEN半合子或纯合子缺失发生。Gleason分级为3的腺体在基因上是异质性的，一些含有与Gleason分级为4的腺体中观察到的相同基因改变。
