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DNA hypermethylation: when tumour suppressor genes go silent.DNA高甲基化:当肿瘤抑制基因沉默时。
Hum Genet. 2002 Aug;111(2):115-27. doi: 10.1007/s00439-002-0783-6. Epub 2002 Jul 16.
2
Treatment of cancer cells with methioninase produces DNA hypomethylation and increases DNA synthesis.用甲硫氨酸酶处理癌细胞会导致DNA低甲基化并增加DNA合成。
Cancer Res. 2002 Aug 15;62(16):4685-9.
3
CpG methylation modifies the genetic stability of cloned repeat sequences.CpG甲基化修饰克隆重复序列的遗传稳定性。
Genome Res. 2002 Aug;12(8):1246-56. doi: 10.1101/gr.74502.
4
Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability.散发性微卫星不稳定型乳腺癌中错配修复基因hMSH2和hMLH1的遗传与表观遗传修饰
Oncogene. 2002 Aug 22;21(37):5696-703. doi: 10.1038/sj.onc.1205683.
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Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma.胃腺瘤中APC基因突变与腺癌发生之间的负相关关系。
Am J Pathol. 2002 Aug;161(2):611-8. doi: 10.1016/S0002-9440(10)64216-2.
6
Reactivating the expression of methylation silenced genes in human cancer.重新激活人类癌症中甲基化沉默基因的表达。
Oncogene. 2002 Aug 12;21(35):5496-503. doi: 10.1038/sj.onc.1205602.
7
5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy.5-氮杂胞苷和5-氮杂-2'-脱氧胞苷作为DNA甲基化抑制剂:作用机制研究及其对癌症治疗的意义
Oncogene. 2002 Aug 12;21(35):5483-95. doi: 10.1038/sj.onc.1205699.
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DNA methylation in cancer: too much, but also too little.癌症中的DNA甲基化:过多,但也过少。
Oncogene. 2002 Aug 12;21(35):5400-13. doi: 10.1038/sj.onc.1205651.
9
DNA methylation and cancer.DNA甲基化与癌症。
Oncogene. 2002 Aug 12;21(35):5358-60. doi: 10.1038/sj.onc.1205597.
10
Genetic instability in human mismatch repair deficient cancers.人类错配修复缺陷型癌症中的基因不稳定
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微卫星不稳定的胃癌中hMLH1的突变与甲基化

Mutation and methylation of hMLH1 in gastric carcinomas with microsatellite instability.

作者信息

Fang Dian-Chun, Wang Rong-Quan, Yang Shi-Ming, Yang Jian-Ming, Liu Hai-Feng, Peng Gui-Yong, Xiao Tian-Li, Luo Yuan-Hui

机构信息

Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

出版信息

World J Gastroenterol. 2003 Apr;9(4):655-9. doi: 10.3748/wjg.v9.i4.655.

DOI:10.3748/wjg.v9.i4.655
PMID:12679904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4611422/
Abstract

AIM

To appraise the correlation of mutation and methylation of hMSH1 with microsatellite instability (MSI) in gastric cancers.

METHODS

Mutation of hMLH1 was detected by Two-dimensional electrophoresis (Two-D) and DNA sequencing; Methylation of hMLH1 promoter was measured with methylation-specific PCR; MSI was analyzed by PCR-based methods.

RESULTS

Sixty-eight cases of sporadic gastric carcinoma were studied for mutation and methylation of hMLH1 promoter and MSI. Three mutations were found, two of them were caused by a single bp substitution and one was caused by a 2 bp substitution, which displayed similar Two-D band pattern. Methylation of hMLH1 promoter was detected in 11(16.2 %) gastric cancer. By using five MSI markers, MSI in at least one locus was detected in 17/68(25 %) of the tumors analyzed. Three hMLH1 mutations were all detected in MSI-H (>=2 loci, n=8), but no mutation was found in MSI-L (only one locus, n=9) or MSS (tumor lacking MSI or stable, n=51). Methylation frequency of hMLH1 in MSI-H (87.5 %, 7/8) was significantly higher than that in MSI-L (11.1 %, 1/9) or MSS (5.9 %, 3/51) (P<0.01-0.001), but no difference was found between MSI-L and MSS (P>0.05).

CONCLUSION

Both mutation and methylation of hMLH1 are involved in the MSI pathway but not related to the LOH pathway in gastric carcinogenesis.

摘要

目的

评估胃癌中hMSH1的突变和甲基化与微卫星不稳定性(MSI)的相关性。

方法

采用二维电泳(Two-D)和DNA测序检测hMLH1的突变;用甲基化特异性PCR检测hMLH1启动子的甲基化;通过基于PCR的方法分析MSI。

结果

对68例散发性胃癌进行hMLH1启动子的突变、甲基化及MSI研究。发现3个突变,其中2个由单个碱基替换引起,1个由2个碱基替换引起,它们显示出相似的二维电泳条带模式。11例(16.2%)胃癌检测到hMLH1启动子甲基化。使用5个MSI标记,在17/68(25%)分析的肿瘤中至少1个位点检测到MSI。3个hMLH1突变均在MSI-H(≥2个位点,n = 8)中检测到,但在MSI-L(仅1个位点,n = 9)或MSS(无MSI或稳定的肿瘤,n = 51)中未发现突变。hMLH1在MSI-H中的甲基化频率(87.5%,7/8)显著高于MSI-L(11.1%,1/9)或MSS(5.9%,3/51)(P<0.01 - 0.001),但MSI-L和MSS之间无差异(P>0.05)。

结论

hMLH1的突变和甲基化均参与胃癌发生的MSI途径,但与LOH途径无关。