Possible role of telomerase activation in the cancer predisposition of patients with hereditary nonpolyposis colorectal cancers
Possible role of telomerase activation in the cancer predisposition of patients with hereditary nonpolyposis colorectal cancers
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DOI：
10.1093/jnci/90.4.316
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发表时间：
1998-02-18
期刊：
影响因子：
--
通讯作者：
Wang, TCV
中科院分区：
文献类型：
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作者：
Cheng, AJ;Tang, RP;Wang, TCV
背景：遗传性非息肉病性结直肠癌综合征(HNPCC综合征；又称Lynch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的胚系突变所致，这些蛋白质的缺陷使突变在DNA中积累得更快，并影响癌症的发展速度。最近的研究表明，参与染色体末端合成的一种酶在体细胞中的活性重新激活可能在肿瘤的发生中起作用。在本研究中，我们检测了HNPCC和非HNPCC患者的正常和癌变组织中端粒酶的表达。方法：采用聚合酶链式反应-端粒重复序列扩增技术检测33例非HNPCC患者(23例正常、26例息肉和37例癌组织)和24例HNPCC患者(24例正常、0例息肉和28例癌组织)的端粒酶活性。结果：18例非HNPCC患者37例癌组织标本中31例端粒酶阳性，24例HNPCC患者28例癌组织标本中27例端粒酶阳性，23例非HNPCC患者23例正常粘膜标本中仅1例端粒酶阳性，24例HNPCC患者24例正常粘膜标本中8例端粒酶阳性；两组之间的差异具有统计学意义(双侧P=.0226)，暗示：这项研究产生了这样的假设，即HNPCC综合征患者的基因缺陷有助于端粒酶活性的重新激活，这一过程可能与他们患癌症的易感性有关。
Background: 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, Methods: 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), Results: 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), Implication: 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.