Journal article

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Kate Lawrenson, Qiyan Li, Siddhartha Kar, Ji-Heui Seo, Jonathan Tyrer, Tassja J Spindler, Janet Lee, Yibu Chen, Alison Karst, Ronny Drapkin, Katja KH Aben, Hoda Anton-Culver, Natalia Antonenkova, Helen Baker, Elisa V Bandera, Yukie Bean, Matthias W Beckmann, Andrew Berchuck, Maria Bisogna, Line Bjorge Show all

Nature Communications | NATURE RESEARCH | Published : 2015

Abstract

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conform..

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Grants

Awarded by European Commission


Awarded by Ovarian Cancer Research Fund


Awarded by US National Cancer Institute (NCI) GAME-ON Post-GWAS Initiative


Awarded by Wellcome Trust


Awarded by Cancer Research UK


Awarded by The Francis Crick Institute


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

Grant Support-higher level funding: the COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute (NCI) GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Project established by the NCI and National Human Genome Research Institute.