Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
J Cell Mol Med. 2011 Jun;15(6):1227-38. doi: 10.1111/j.1582-4934.2011.01284.x.
The role telomeres and telomerase play in the initiation and progression of human cancers has been extensively evaluated. Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere-associated proteins, including the six member Shelterin complex. The main function of the telomere is to stabilize the ends of the chromosomes. However, through multiple mechanisms, telomeres can become dysfunctional, which may drive genomic instability leading to the development of cancer. The majority of human cancers maintain, or actively lengthen, telomeres through up-regulation of the reverse transcriptase telomerase. Because there are significant differences in telomere length and telomerase activity between malignant and non-malignant tissues, many investigations have assessed the potential to utilize these molecular markers for cancer diagnosis. Here, we critically evaluate whether measurements of telomere lengths and telomerase levels may be clinically utilized as diagnostic markers in solid tumours, with emphasis on breast and prostate cancer as representative examples. Future directions focusing on the direct detection of dysfunctional telomeres are explored. New markers for telomere dysfunction may eventually prove clinically useful.
端粒和端粒酶在人类癌症的发生和发展中的作用已经得到了广泛的评估。端粒是由六聚体 DNA 重复序列 TTAGGG 和许多端粒相关蛋白组成的核蛋白复合物，包括六个成员的 Shelterin 复合物。端粒的主要功能是稳定染色体的末端。然而，通过多种机制，端粒可能会失去功能，这可能会导致基因组不稳定，从而导致癌症的发展。大多数人类癌症通过逆转录酶端粒酶的上调来维持或积极延长端粒。由于恶性和非恶性组织之间的端粒长度和端粒酶活性存在显著差异，许多研究评估了利用这些分子标志物进行癌症诊断的潜力。在这里，我们批判性地评估了测量端粒长度和端粒酶水平是否可以作为实体瘤的临床诊断标志物，重点关注乳腺癌和前列腺癌作为代表性示例。探讨了专注于检测功能失调端粒的直接检测的未来方向。端粒功能失调的新标志物最终可能具有临床应用价值。
