期刊
CELL DISCOVERY
卷 7, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41421-021-00342-6
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资金
- Chinese National Key Research and Development Project [2018YFC1315600]
- National Natural Science Foundation of China [82003544, 81973113, 81320108022, 81502877, 81972431, 31871327, 32070675]
- Program for Changjiang Scholars and Innovative Research Team in University in China [IRT_14R40]
- Natural Science Foundation of Tianjin [16JCYBJC26600, 18YFZCSY00520, 19JCJQJC63600]
- National Foundation for Cancer Research, a Hanes and Wills Family endowed professorship in cancer at the Wake Forest Baptist Comprehensive Cancer Center
Survival rates for ovarian cancer patients can vary significantly, with a study in 2130 Chinese patients identifying a new genetic locus associated with overall survival. Through further analysis, researchers pinpointed a potentially causal SNP and a lncRNA that may regulate tumor growth.
Ovarian cancer survival varies considerably among patients, to which germline variation may also contribute in addition to mutational signatures. To identify genetic markers modulating ovarian cancer outcome, we performed a genome-wide association study in 2130 Chinese ovarian cancer patients and found a hitherto unrecognized locus at 3p26.1 to be associated with the overall survival (P-combined = 8.90 x 10(-10)). Subsequent statistical fine-mapping, functional annotation, and eQTL mapping prioritized a likely casual SNP rs9311399 in the non-coding regulatory region. Mechanistically, rs9311399 altered its enhancer activity through an allele-specific transcription factor binding and a long-range interaction with the promoter of a lncRNA BHLHE40-AS1. Deletion of the rs9311399-associated enhancer resulted in expression changes in several oncogenic signaling pathway genes and a decrease in tumor growth. Thus, we have identified a novel genetic locus that is associated with ovarian cancer survival possibly through a long-range gene regulation of oncogenic pathways.
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