对接受初次肿瘤细胞减灭术的卵巢癌患者进行全基因组关联分析，以确定残留疾病的候选基因。
Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.
作者信息
Ramachandran Dhanya, Tyrer Jonathan P, Kommoss Stefan, DeFazio Anna, Riggan Marjorie J, Webb Penelope M, Fasching Peter A, Lambrechts Diether, García María J, Rodríguez-Antona Cristina, Goodman Marc T, Modugno Francesmary, Moysich Kirsten B, Karlan Beth Y, Lester Jenny, Kjaer Susanne K, Jensen Allan, Høgdall Estrid, Goode Ellen L, Cliby William A, Kumar Amanika, Wang Chen, Cunningham Julie M, Winham Stacey J, Monteiro Alvaro N, Schildkraut Joellen M, Cramer Daniel W, Terry Kathryn L, Titus Linda, Bjorge Line, Thomsen Liv Cecilie Vestrheim, Pejovic Tanja, Høgdall Claus K, McNeish Iain A, May Taymaa, Huntsman David G, Pfisterer Jacobus, Canzler Ulrich, Park-Simon Tjoung-Won, Schröder Willibald, Belau Antje, Hanker Lars, Harter Philipp, Sehouli Jalid, Kimmig Rainer, de Gregorio Nikolaus, Schmalfeldt Barbara, Baumann Klaus, Hilpert Felix, Burges Alexander, Winterhoff Boris, Schürmann Peter, Speith Lisa-Marie, Hillemanns Peter, Berchuck Andrew, Johnatty Sharon E, Ramus Susan J, Chenevix-Trench Georgia, Pharoah Paul D P, Dörk Thilo, Heitz Florian
机构信息
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
出版信息
NPJ Genom Med. 2024 Mar 5;9(1):19. doi: 10.1038/s41525-024-00395-y.
Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
卵巢癌的生存情况取决于初次手术后的切除状态。我们对7705例卵巢癌患者（包括4954例高级别浆液性癌患者）的切除状态进行了全基因组关联分析，以确定与残留疾病相关的变异。在高级别浆液性癌中，观察到与切除状态最显著的关联是位于MGMT上游的rs72845444（p = 3.9×10）。在基于基因的分析中，经过分期调整后，PPP2R5C是高级别浆液性癌中关联最强的基因。在AGO-OVAR 11研究的一组独立的378例卵巢肿瘤中，MGMT和PPP2R5C附近的变异与甲基化和转录水平相关，并且PPP2R5C mRNA水平可预测残留疾病患者的无进展生存期。MGMT编码一种DNA修复酶，PPP2R5C编码PP2A肿瘤抑制因子的B56γ亚基。我们的研究结果将这两个基因座的遗传变异与高级别浆液性癌的切除状态联系起来。
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