MLH1
微卫星不稳定性
医学
乳腺癌
彭布罗利珠单抗
林奇综合征
肿瘤科
内科学
癌症
杂合子丢失
MSH2
结直肠癌
癌症研究
DNA错配修复
生物
遗传学
微卫星
等位基因
免疫疗法
基因
作者
Henry G. Kaplan,Jeffrey R. Whiteaker,Brianna Nelson,Richard G. Ivey,Travis D. Lorentzen,Uliana J. Voytovich,Lei Zhao,David J. Corwin,Robert G. Resta,Amanda G. Paulovich
出处
期刊:Journal of The National Comprehensive Cancer Network
日期:2023-08-29
卷期号:: 1-7
标识
DOI:10.6004/jnccn.2023.7035
摘要
A woman with estrogen/progesterone receptor-positive, ERBB2-negative metastatic breast cancer developed progressive disease despite treatment with multiple hormonal and chemotherapeutic modalities. She carried a germline variant of MLH1 (1835del3), also known as c.1835_1837del and v612del, the pathogenicity of which has not been conclusively determined. MLH1 staining was not seen on immunohistochemical staining of her tumor tissue. The patient experienced a >5-year dramatic response to 4 doses of pembrolizumab. Family studies revealed multiple other relatives with the MLH1 1835del3 variant, as well as multiple relatives with colon cancer. The one relative with colon cancer who underwent genetic testing demonstrated the same variant. Laboratory studies revealed that the patient's tumor showed loss of heterozygosity (LOH) in the MLH1 region, high levels of microsatellite instability, and a high tumor mutational burden. LOH in the MLH1 region, along with the remarkable clinical response to pembrolizumab treatment and the presence of the same MLH1 variant in affected relatives, supports the hypothesis that the MLH1 1835del3 variant is pathogenic. Given the patient's family history, this likely represents an uncommon presentation of Lynch syndrome. Physicians should be alert to evaluate patients for targetable genetic variants even in unlikely clinical situations such as the one described here.
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