同源重组缺陷末期高级别浆液性卵巢癌的多组学分析。
Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.
发表日期：2023 Feb 27
作者：
Nikki L Burdett, Madelynne O Willis, Kathryn Alsop, Allison L Hunt, Ahwan Pandey, Phineas T Hamilton, Tamara Abulez, Xuan Liu, Therese Hoang, Stuart Craig, Sian Fereday, Joy Hendley, Dale W Garsed, Katy Milne, Shreena Kalaria, Ashley Marshall, Brian L Hood, Katlin N Wilson, Kelly A Conrads, Kathleen I Pishas, Sumitra Ananda, Clare L Scott, Yoland Antill, Orla McNally, Linda Mileshkin, Anne Hamilton, George Au-Yeung, Lisa Devereux, Heather Thorne, Andrea Bild, Nicholas W Bateman, G Larry Maxwell, Jeffrey T Chang, Thomas P Conrads, Brad H Nelson, David D L Bowtell, Elizabeth L Christie
来源：
NATURE GENETICS
摘要：
高级别浆液性卵巢癌（HGSC）通常具有同源重组（HR）DNA修复缺陷，虽然大多数这样的肿瘤对初始治疗敏感，但获得性抗药性很普遍。我们采用多组学方法，使用从15名HR缺陷HGSC患者的多个尸检样本进行了分子多样性研究。患者存在多克隆性疾病，并在大多数患者中发现了几种耐药机制，包括还原突变和其他方式的HR恢复。我们还观察到频繁的全基因组重复和免疫组成的全局改变，证明存在免疫逃逸现象。该分析突显了HGSC内多样的进化变化，这些变化能够逃避治疗并最终压倒患者。© 2023年作者，独家授权Springer Nature America，Inc.
High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.