Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma

Angel Chao, Chyong Huey Lai, Tzu Hao Wang, Shih Ming Jung, Yun Shien Lee, Wei Yang Chang, Lan Yang Yang, Fei Chun Ku, Huei Jean Huang, An Shine Chao, Chin Jung Wang, Ting Chang Chang, Ren Chin Wu*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

17 引文 斯高帕斯(Scopus)

摘要

Abstract: We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Key messages: Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC.Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC.LOH score is the strongest adverse prognostic factor in patients with OCCC.

原文英語
頁(從 - 到)527-536
頁數10
期刊Journal of Molecular Medicine
96
發行號6
DOIs
出版狀態已出版 - 01 06 2018

文獻附註

Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

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