Assessment of mismatch repair deficiency in ovarian cancer.
Assessment of mismatch repair deficiency in ovarian cancer.
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DOI：
10.1136/jmedgenet-2020-107270
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发表时间：
2021-10
影响因子：
4
通讯作者：
Evans DG
中科院分区：
文献类型：
--
作者：
Crosbie EJ;Ryan NAJ;McVey RJ;Lalloo F;Bowers N;Green K;Woodward ER;Clancy T;Bolton J;Wallace AJ;McMahon RF;Evans DG
卵巢癌的遗传原因包括Lynch综合征，这是由于遗传致病性变异影响了参与DNA修复的四个错配修复基因中的一个。本研究的目的是评估肿瘤错配修复缺陷和林奇综合征的患病率高危妇女转介到曼彻斯特基因组医学中心卵巢癌在过去的20年。35岁前诊断为卵巢癌和/或有Lynch综合征癌症个人或家族史的女性接受错配修复缺陷免疫组化肿瘤检测，如有必要，进行MLH1启动子甲基化检测，然后进行Lynch综合征体质检测。共检测了261例卵巢癌，其中27例（10.3%;95% CI 6.9%至14.7%）免疫组化显示错配修复缺陷。7名MLH1缺失患者中有3名显示MLH1启动子超甲基化，其余24名中有18名接受了Lynch综合征的体质检测。另外15名患有错配修复熟练肿瘤的妇女由于有强烈的Lynch综合征癌症家族史而接受了体质测试。在33-59岁（中位48岁）接受体质检测的9/33（27%）女性中发现了致病变异，其中包括一名肿瘤错配修复熟练的患者。Lynch综合征肿瘤多为子宫内膜样组织学亚型。肿瘤错配修复缺陷的免疫组织化学鉴定是一个有用的预筛选卵巢癌妇女的体质测试，个人或家族史提示林奇综合征。
Hereditary causes of ovarian cancer include Lynch syndrome, which is due to inherited pathogenic variants affecting one of the four mismatch repair genes involved in DNA repair. The aim of this study was to evaluate tumour mismatch repair deficiency and prevalence of Lynch syndrome in high-risk women referred to the Manchester Centre for Genomic Medicine with ovarian cancer over the past 20 years. Women with ovarian cancer diagnosed before the age of 35 years and/or with a suggestive personal or family history of Lynch syndrome cancers underwent tumour testing with immunohistochemistry for mismatch repair deficiency and, where indicated, MLH1 promoter methylation testing followed by constitutional testing for Lynch syndrome. In total, 261 ovarian cancers were tested and 27 (10.3%; 95% CI 6.9% to 14.7%) showed mismatch repair deficiency by immunohistochemistry. Three of 7 with MLH1 loss showed MLH1 promoter hypermethylation, and 18 of the remaining 24 underwent constitutional testing for Lynch syndrome. A further 15 women with mismatch repair proficient tumours underwent constitutional testing because of a strong family history of Lynch syndrome cancers. Pathogenic variants were identified in 9/33 (27%) women who underwent constitutional testing, aged 33–59 years (median 48 years), including one whose tumour was mismatch repair proficient. Most Lynch syndrome tumours were of endometrioid histological subtype. Tumour mismatch repair deficiency identified by immunohistochemistry is a useful prescreen for constitutional testing in women with ovarian cancer with personal or family histories suggestive of Lynch syndrome.
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影响因子：
8.8
作者：
Dominguez-Valentin, Mev;Sampson, Julian R.;Moller, Pal
通讯作者：
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作者：
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通讯作者：
Evans, D. G.