Mismatch repair and treatment resistance in ovarian cancer.
Mismatch repair and treatment resistance in ovarian cancer.
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DOI：
10.1186/1471-2407-6-201
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发表时间：
2006-07-31
期刊：
影响因子：
3.8
通讯作者：
Berns EM
中科院分区：
文献类型：
--
作者：
Helleman J;van Staveren IL;Dinjens WN;van Kuijk PF;Ritstier K;Ewing PC;van der Burg ME;Stoter G;Berns EM
卵巢癌的治疗受到对铂类化疗的内在或获得性耐药性的阻碍。本研究的目的是确定错配修复（MMR）失活在卵巢癌中的频率及其与铂类化疗耐药的关系。我们确定，微卫星不稳定性（MSI）作为MMR失活的标志（分析BAT 25和BAT 26），MLH 1启动子甲基化状态（对亚硫酸氢盐处理的DNA的甲基化特异性PCR）和MLH 1，MSH 2，MSH 3，msh和pms 2应用RT-PCR方法对75例卵巢癌和8株卵巢癌细胞系进行了MSI检测，其中3株细胞系A2780为MSI阳性（由于启动子甲基化而没有MLH 1 mRNA表达）、SKOV 3（没有MLH 1 mRNA表达）和2774（没有改变的MMR基因表达）。总体而言，在这8个细胞系中，顺铂反应与MMR状态之间没有关联。75例卵巢癌中有7例显示MLH 1启动子甲基化，但均未显示MSI。其中46例患者接受了含铂化疗（11例无应答者，34例应答者，1例应答未知）。在11例无应答者中观察到的耐药与MSI无关，因此也与MMR失活无关。在75例卵巢癌标本中未检测到MMR失活，并且在卵巢癌细胞系以及卵巢癌中未发现MMR失活与耐药之间的关联。在讨论中，将结果与文献中的20项类似研究（共1315例卵巢癌患者）的结果进行比较。虽然在原发性肿瘤中没有观察到反应和MMR状态之间的关联，但MMR失活在获得性耐药中的可能作用值得进一步研究。
The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.
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DOI：
10.1093/jnci/89.20.1537
发表时间：
1997-10-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
delasAlas, MM;Aebi, S;Los, G
通讯作者：
Los, G
影响因子：
11.5
作者：
Gifford, G;Paul, J;Brown, R
通讯作者：
Brown, R
影响因子：
4.7
作者：
Arzimanoglou, II;Lallas, T;Gilbert, F
通讯作者：
Gilbert, F
影响因子：
8
作者：
Deng, GR;Chen, A;Kim, YS
通讯作者：
Kim, YS
影响因子：
4.8
作者：
Drummond, JT;Anthoney, A;Modrich, P
通讯作者：
Modrich, P