全球精选文摘 - MLH1和 MSH2在Lynch综合征中的预测作用

高级搜索

免费注册

首页

期刊文献

全球精选文摘

中国作者重要发表

爱思唯尔期刊精选全文

柳叶刀中文版精选全文

2009年诺贝尔奖得主文章

成功投稿经验系列访谈

2010年度诺贝尔奖得主

医药资讯

医学资讯

药品动态

诊疗指南

病例分析

数据库

会议精粹

柳叶刀流感峰会

2009世界高血压大会

辉瑞中国医学研究高峰论坛

上海东方呼吸病国际论坛

GAP-CCBC系列会议

精品书籍

爱思唯尔参考书

新书订购活动

疾病资源

专家博客

当前位置 > > > >

MLH1和 MSH2在Lynch综合征中的预测作用

Prediction of MLH1 and MSH2 Mutations in Lynch Syndrome

Balmaña J, Stockwell DH, Steyerberg EW 2009/5/27 10:50:40

【发表评论】【全球专家评论】

打印| 推荐给好友

JAMA, 2006,

专家评级：

★★

循证评级：

View at Publisher

Abstract

Context:

Lynch syndrome is caused primarily by mutations in the mismatch repair genes MLH1 and MSH2.

Objectives:

To analyze MLH1/MSH2 mutation prevalence in a large cohort of patients undergoing genetic testing and to develop a clinical model to predict the likelihood of finding a mutation in at-risk patients.

Design, Setting, and Participants:

Personal and family history were obtained for 1914 unrelated probands who submitted blood samples starting in the year 2000 for full gene sequencing of MLH1/MSH2. Genetic analysis was performed using a combination of sequence analysis and Southern blotting. A multivariable model was developed using logistic regression in an initial cohort of 898 individuals and subsequently prospectively validated in 1016 patients. The complex model that we have named PREMM1,2 (Prediction of Mutations in MLH1 and MSH2) was developed into a Web-based tool that incorporates personal and family history of cancer and adenomas.

Main Outcome Measure:

Deleterious mutations in MLH1/MSH2 genes.

Results:

Overall, 14.5% of the probands (130/898) carried a pathogenic mutation (MLH1, 6.5%; MSH2, 8.0%) in the development cohort and 15.3% (155/1016) in the validation cohort, with 42 (27%) of the latter being large rearrangements. Strong predictors of mutations included pro-band characteristics (presence of colorectal cancer, especially ≥ 2 separate diagnoses, or endometrial cancer) and family history (especially the number of first-degree relatives with colorectal or endometrial cancer). Age at diagnosis was particularly important for colorectal cancer. The multivariable model discriminated well at external validation, with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval, 0.76–0.84).

Conclusions:

Personal and family history characteristics can accurately predict the outcome of genetic testing in a large population at risk of Lynch syndrome. The PREMM1,2 model provides clinicians with an objective, easy-to-use tool to estimate the likelihood of finding mutations in the MLH1/MSH2 genes and may guide the strategy for molecular evaluation.

请登录后发表评论，点击此处登录。

全部学科

疾病资源中心

高血压	慢性阻塞性肺病
脂肪性肝病	糖尿病
卒中	肺癌
冠心病	子宫内膜异位症
结直肠癌	乳腺癌
心力衰竭	心律失常

病例分析 [栏目介绍]

甲状腺功能亢进合并黄疸

王燕燕王曙

上海交通大学附属瑞金医院内分泌科

患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。

更多>>>

医学数据库