Cheng A J, Tang R, Wang J Y, See L C, Wang T C
Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Taiwan, Republic of China.
J Natl Cancer Inst. 1998 Feb 18;90(4):316-21. doi: 10.1093/jnci/90.4.316.
Hereditary nonpolyposis colorectal cancer syndrome (HNPCC syndrome; also called Lynch syndrome) is one of the most common cancer predisposition syndromes. Most cases of cancer associated with this syndrome are due to the inheritance of germline mutations in genes that encode proteins required for DNA mismatch repair; defects in these proteins allow mutations to accumulate more rapidly in the DNA and influence the rate of cancer development. Recent studies indicate that the reactivation of the activity of telomerase, an enzyme involved in the synthesis of chromosomal ends, in somatic cells may play a role in carcinogenesis. In this study, we evaluated the expression of telomerase in normal and cancerous colorectal tissue specimens from HNPCC and non-HNPCC patients.
The polymerase chain reaction-based telomeric repeat amplification protocol was used to assay telomerase activity in colorectal tissue specimens from 33 non-HNPCC patients (23 normal, 26 polyps, and 37 cancer specimens) and from 24 HNPCC patients (24 normal, 0 polyps, and 28 cancer specimens).
Thirty-one of 37 carcinoma samples from 18 non-HNPCC patients and 27 of 28 carcinoma samples from 24 HNPCC patients were found to be positive for telomerase activity. Whereas only one of 23 normal mucosa samples from 23 non-HNPCC patients was found to have (weak) telomerase activity, eight of 24 normal mucosa samples from 24 HNPCC patients were positive for telomerase; the difference between the two groups was statistically significant (two-sided P = .0226).
This study generates the hypothesis that genetic defects in individuals with HNPCC syndrome facilitate the reactivation of telomerase activity, a process which may be associated with their predisposition to develop cancer.
遗传性非息肉病性结直肠癌综合征（HNPCC综合征；也称为林奇综合征）是最常见的癌症易感综合征之一。与该综合征相关的大多数癌症病例是由于编码DNA错配修复所需蛋白质的基因发生种系突变遗传所致；这些蛋白质的缺陷会使DNA中的突变积累得更快，并影响癌症的发展速度。最近的研究表明，端粒酶（一种参与染色体末端合成的酶）在体细胞中的活性重新激活可能在致癌过程中起作用。在本研究中，我们评估了HNPCC患者和非HNPCC患者正常及癌性结直肠组织标本中端粒酶的表达。
采用基于聚合酶链反应的端粒重复序列扩增方案，检测33例非HNPCC患者（23例正常组织、26例息肉和37例癌组织标本）和24例HNPCC患者（24例正常组织、0例息肉和28例癌组织标本）结直肠组织标本中端粒酶的活性。
在18例非HNPCC患者的37份癌组织样本中，有31份端粒酶活性呈阳性；在24例HNPCC患者的28份癌组织样本中，有27份端粒酶活性呈阳性。而在23例非HNPCC患者的23份正常黏膜样本中，只有1份具有（弱）端粒酶活性；在24例HNPCC患者的24份正常黏膜样本中，有8份端粒酶呈阳性；两组之间的差异具有统计学意义（双侧P = 0.0226）。
本研究提出了一个假设，即HNPCC综合征患者的基因缺陷促进了端粒酶活性的重新激活，这一过程可能与他们患癌的易感性有关。
