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DNA错配修复缺陷宿主的肿瘤在基因组不稳定性方面表现出显著增加。

Tumors of DNA mismatch repair-deficient hosts exhibit dramatic increases in genomic instability.

作者信息

Baross-Francis A, Andrew S E, Penney J E, Jirik F R

机构信息

Center for Molecular Medicine and Therapeutics, and Department of Medicine, University of British Columbia, Vancouver, BC Canada V5Z 4H4.

出版信息

Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8739-43. doi: 10.1073/pnas.95.15.8739.

DOI:10.1073/pnas.95.15.8739
PMID:9671748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC21146/
Abstract

DNA mismatch repair (MMR) deficiency is associated with an increased mutational burden and predisposition to certain malignancies. Relatively little is known, however, about gene-specific mutation frequencies within MMR-deficient primary tumors. Thymic lymphomas from Msh2(-/-) mice were thus analyzed by using a lacI-based transgenic shuttle-phage mutation detection system. All tumors exhibited greatly elevated lacI gene mutation frequencies, ranging from 3.2- to 17.4-fold above the approximately 15-fold elevations present within normal Msh2(-/-) thymi. In addition, lacI genes harboring multiple changes, including clusters of mutations, were found in thymic tumor DNA. The results suggest that an additional mutator activity, such as an error-prone DNA polymerase, leads to increased genomic instability in these MMR-deficient tumors.

摘要

DNA错配修复（MMR）缺陷与突变负担增加以及某些恶性肿瘤的易感性相关。然而，关于MMR缺陷原发性肿瘤内基因特异性突变频率，人们了解相对较少。因此，通过使用基于lacI的转基因穿梭噬菌体突变检测系统，对Msh2(-/-)小鼠的胸腺淋巴瘤进行了分析。所有肿瘤均表现出lacI基因突变频率大幅升高，比正常Msh2(-/-)胸腺中约15倍的升高幅度还要高3.2至17.4倍。此外，在胸腺肿瘤DNA中发现了携带多种变化（包括突变簇）的lacI基因。结果表明，一种额外的诱变活性，如易出错的DNA聚合酶，导致这些MMR缺陷肿瘤中的基因组不稳定性增加。

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本文引用的文献

1
Tissues of MSH2-deficient mice demonstrate hypermutability on exposure to a DNA methylating agent.MSH2基因缺陷小鼠的组织在暴露于DNA甲基化剂时表现出高突变性。
Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1126-30. doi: 10.1073/pnas.95.3.1126.
2
Transient expression of a mutator phenotype in cancer cells.癌细胞中突变体表型的瞬时表达。
Science. 1997 Sep 5;277(5331):1449-50. doi: 10.1126/science.277.5331.1449.
3
Conditional mutator phenotypes in hMSH2-deficient tumor cell lines.人源错配修复蛋白2（hMSH2）缺陷型肿瘤细胞系中的条件性突变体表型
Science. 1997 Sep 5;277(5331):1523-6. doi: 10.1126/science.277.5331.1523.
4
Base transitions dominate the mutational spectrum of a transgenic reporter gene in MSH2 deficient mice.在 MSH2 基因缺陷小鼠中，碱基转换在转基因报告基因的突变谱中占主导地位。
Oncogene. 1997 Jul 10;15(2):123-9. doi: 10.1038/sj.onc.1201180.
5
Spectra of spontaneous mutations at the hprt locus in colorectal carcinoma cell lines defective in mismatch repair.错配修复缺陷的结肠癌细胞系中hprt基因座的自发突变谱。
Carcinogenesis. 1997 Jun;18(6):1127-33. doi: 10.1093/carcin/18.6.1127.
6
Cancer-susceptibility genes. Gatekeepers and caretakers.癌症易感基因。守门基因和维持基因。
Nature. 1997 Apr 24;386(6627):761, 763. doi: 10.1038/386761a0.
7
DNA mismatch repair deficient mice in cancer research.癌症研究中DNA错配修复缺陷小鼠
Semin Cancer Biol. 1996 Oct;7(5):241-7. doi: 10.1006/scbi.1996.0032.
8
Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects.具有特定错配修复基因缺陷的人类癌细胞系中次黄嘌呤磷酸核糖转移酶（hprt）基因座的突变率。
Carcinogenesis. 1997 Jan;18(1):1-8. doi: 10.1093/carcin/18.1.1.
9
Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype.微卫星突变体表型的结肠癌中BAX基因的体细胞移码突变
Science. 1997 Feb 14;275(5302):967-9. doi: 10.1126/science.275.5302.967.
10
Mutator specificity and disease: looking over the FENce.突变特异性与疾病：审视FENce
Cell. 1997 Jan 24;88(2):155-8. doi: 10.1016/s0092-8674(00)81832-2.