Journal article
Mutation of FOXL2 in granulosa-cell tumors of the ovary
SP Shah, M Köbel, J Senz, RD Morin, BA Clarke, KC Wiegand, G Leung, A Zayed, E Mehl, SE Kalloger, M Sun, R Giuliany, E Yorida, S Jones, R Varhol, KD Swenerton, D Miller, PB Clement, C Crane, J Madore Show all
New England Journal of Medicine | MASSACHUSETTS MEDICAL SOC | Published : 2009
Abstract
BACKGROUND: Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The pathogenesis of these tumors is unknown. Moreover, their histopathological diagnosis can be challenging, and there is no curative treatment beyond surgery. METHODS: We analyzed four adult-type GCTs using whole-transcriptome paired-end RNA sequencing. We identified putative GCT-specific mutations that were present in at least three of these samples but were absent from the transcriptomes of 11 epithelial ovarian tumors, published human genomes, and databases of single-nucleotide polymorphisms. We confirmed these variants by direct sequencing of complementary DNA and genomi..
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Awarded by Medical Research and Materiel Command
Funding Acknowledgements
Supported by grants from the British Columbia Cancer Foundation and the Vancouver General Hospital Foundation (to OvCaRe in British Columbia), Genome Canada (to the Genome Sciences Centre), the Michael Smith Foundation for Health Research (to OvCaRe and the Genome Sciences Centre and to Drs. Shah, Marra, and Huntsman), Eli Lilly Canada (to Dr. Kobel), and the Canadian Institutes of Health Research's Training Program on Clinician-Scientists in Molecular Oncologic Pathology (to Dr. Turashvili); nondirected research funds from Sanofi-Aventis (to the Genetic Pathology Evaluation Centre); and funding for a Canada Research Chair in Molecular Oncology (to Dr. Aparicio). The contributing tumor banks were supported by OvCaRe and Ovarian Cancer Canada (Vancouver General Hospital), Fonds de la Recherche en Sante du Quebec (Montreal), and Ovarian Cancer Canada (Ottawa). The Westmead Gynaecological Oncology Tissue Bank is a member of the Australasian Biospecimens Network-Oncology group, which is funded by the Australian National Health and Medical Research Council; by Cancer Research UK, the University of Cambridge, Hutchinson Whampoa, the Experimental Cancer Medicine Centre, and the National Institute for Health Research's Cambridge Biomedical Research Centre; by a grant (DAMD17-01-1-0729) from the U. S. Army Medical Research and Materiel Command; and by grants from the Cancer Council Tasmania, the Cancer Foundation of Western Australia, and the National Health and Medical Research Council of Australia to the Australian Ovarian Cancer Study. Dr. Kobel reports receiving grant support from Eli Lilly; and Dr. Huntsman, receiving grant support from Sanofi-Aventis and Novartis and being listed as an inventor on a provisional patent application filed by the British Columbia Cancer Agency on the diagnostic use of the FOXL2 402C -> G mutation and its development as a therapeutic target. No other potential conflict of interest relevant to this article was reported. We thank Ying Ng and Katie Chow for performing the array comparative-genomic-hybridization experiments; Krista Marcon for performing the immunohistochemical analysis and preparing tissue sections for DNA extraction; Samuel Leung for establishing the online image archive; Mona Mazgani and Salvador Saldivar for helping in the acquisition of informed consent and specimens for the gynecologic tumor bank at Vancouver General Hospital; Catherine Kennedy for helping in the acquisition of specimens from the Westmead Gynaecological Oncology Tissue Bank; Julie Irving for helping with accessing specimens for the secondary validation; the members of the Australian Ovarian Cancer Study (AOCS) management group: D. Bowtell, G. Chenevix-Trench, A. Green, P. Webb, A. deFazio, and D. Gertig; the AOCS study nurses and research assistants; and all the patients who participated in the AOCS study.