Jerónimo C, Henrique R, Campos P F, Oliveira J, Caballero O L, Lopes C, Sidransky D
Portuguese Oncology Institute, R. Dr. Antonio Bernardino de Almeida, 4200-072 Porto, Portugal.
J Clin Pathol. 2003 Jan;56(1):52-5. doi: 10.1136/jcp.56.1.52.
Alterations in the methylation patterns of promoter CpG islands have been associated with the transcriptional inhibition of genes in many human cancers. These epigenetic alterations could be used as molecular markers for the early detection of cancer-that is, while potentially curable according to current therapeutic strategies. In prostate cancer, GSTP1 hypermethylation is the most common epigenetic alteration, and can be detected in up to 90% of cases. Thus, screening for methylation of other loci would probably increase the number of primary tumours amenable to screening. Moreover, previous studies have shown that the endothelin B receptor (EDNRB) gene is abnormally methylated in a high proportion of prostate tumours ( approximately 70%).
To investigate the potential use of EDNRB gene hypermethylation as a prostate cancer specific marker.
Methylation specific polymerase chain reaction (MSP) for the promoter region of EDNRB was performed on prospectively collected tissue samples from 48 patients harbouring clinically localised prostate cancer, and in a group of 23 patients with benign prostatic hyperplasia (BPH). Genomic DNA was isolated from the samples and the methylation status was examined in a blinded manner.
EDNRB methylation was found in 40 of 48 of the adenocarcinomas. However, the same alteration was found in the paired normal tissue, and 21 of 23 of the BPH samples were found to harbour EDNRB hypermethylation.
EDNRB hypermethylation at CpG sites upstream of the transcription start site can be detected in a high proportion of prostate adenocarcinomas. However, because this same alteration is also present in normal and hyperplastic tissue, it does not distinguish normal from neoplastic prostate cells, thus precluding its use as a prostate cancer marker.
启动子CpG岛甲基化模式的改变与许多人类癌症中基因的转录抑制有关。这些表观遗传改变可作为癌症早期检测的分子标志物，也就是说，根据当前治疗策略，此时癌症可能是可治愈的。在前列腺癌中，GSTP1高甲基化是最常见的表观遗传改变，在高达90%的病例中可检测到。因此，筛查其他位点的甲基化可能会增加适合筛查的原发性肿瘤数量。此外，先前的研究表明，内皮素B受体（EDNRB）基因在高比例的前列腺肿瘤（约70%）中异常甲基化。
研究EDNRB基因高甲基化作为前列腺癌特异性标志物的潜在用途。
对前瞻性收集的48例临床局限性前列腺癌患者的组织样本以及23例良性前列腺增生（BPH）患者进行EDNRB启动子区域的甲基化特异性聚合酶链反应（MSP）。从样本中分离基因组DNA，并以盲法检查甲基化状态。
48例腺癌中有40例发现EDNRB甲基化。然而，在配对的正常组织中也发现了相同的改变，并且在23例BPH样本中有21例发现存在EDNRB高甲基化。
在高比例的前列腺腺癌中可检测到转录起始位点上游CpG位点的EDNRB高甲基化。然而，由于这种相同的改变也存在于正常和增生组织中，它无法区分正常与肿瘤性前列腺细胞，因此不能用作前列腺癌标志物。
