Burdett Nikki L, Willis Madelynne O, Alsop Kathryn, Hunt Allison L, Pandey Ahwan, Hamilton Phineas T, Abulez Tamara, Liu Xuan, Hoang Therese, Craig Stuart, Fereday Sian, Hendley Joy, Garsed Dale W, Milne Katy, Kalaria Shreena, Marshall Ashley, Hood Brian L, Wilson Katlin N, Conrads Kelly A, Pishas Kathleen I, Ananda Sumitra, Scott Clare L, Antill Yoland, McNally Orla, Mileshkin Linda, Hamilton Anne, Au-Yeung George, Devereux Lisa, Thorne Heather, Bild Andrea, Bateman Nicholas W, Maxwell G Larry, Chang Jeffrey T, Conrads Thomas P, Nelson Brad H, Bowtell David D L, Christie Elizabeth L
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Nat Genet. 2023 Mar;55(3):437-450. doi: 10.1038/s41588-023-01320-2. Epub 2023 Feb 27.
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.
高级别浆液性卵巢癌（HGSC）通常具有同源重组（HR）DNA修复缺陷的特征，虽然大多数此类肿瘤对初始治疗敏感，但获得性耐药很常见。我们采用多组学方法来研究终末期疾病中的分子多样性，使用从15名HR缺陷型HGSC女性患者收集的多个尸检样本。患者患有多克隆疾病，并且在大多数患者中鉴定出了几种耐药机制，包括回复突变和通过其他方式恢复HR。我们还观察到频繁的全基因组复制以及免疫组成的整体变化，并伴有免疫逃逸的证据。该分析突出了HGSC内逃避治疗并最终使个体患者不堪重负的多样进化变化。
