Journal article
Identification of fifteen novel germline variants in the BRCA1 3′UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site
BL Brewster, F Rossiello, JD French, SL Edwards, M Wong, A Wronski, P Whiley, N Waddell, X Chen, B Bove, undefined KconFab, JL Hopper, EM John, I Andrulis, M Daly, S Volorio, L Bernard, B Peissel, S Manoukian, M Barile Show all
Human Mutation | WILEY | Published : 2012
DOI: 10.1002/humu.22159
Abstract
Mutations in the BRCA1 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intron-exon boundaries, precluding the identification of mutations in noncoding and untranslated regions (UTR). As 3′UTR mutations can influence cancer susceptibility by altering protein and microRNA (miRNA) binding regions, we screened the BRCA1 3′UTR for mutations in a large series of BRCA-mutation negative, population and clinic-based breast cancer cases, and controls. Fifteen novel BRCA1 3′UTR variants were identified, the majority of which were unique to either cases or controls. Using luciferase reporter assays, three variants foun..
View full abstractGrants
Awarded by National Cancer Institute
Funding Acknowledgements
Contract grant sponsors: National Health Medical Research Council, Australia (#301089; #628333); Cancer Council Queensland, Australia (#631553); Associazione Italiana per la Ricerca sul Cancro (4017); Ministero della Salute, Italy (RFPS-2006-3-340203); Ministero dell'Universita' e Ricerca, Italy (RBLA03-BETH); Istituto Superiore di Sanita', Italy (526D/41); Lega Italiana per la Lotta contro i Tumori, Italy (progetto 02/12/R/47); Fondazione IRCCS Istituto Nazionale Tumori, Italy (INT-Institutional strategic projects '5x1000'); National Institutes of Health, USA under (RFA-CA-06-503); Cancer Care Ontario, Canada (U01 CA69467); Columbia University, USA (U01 CA69398); Fox Chase Cancer Center, USA (U01 CA69631); Huntsman Cancer Institute, USA (U01 CA69446); Cancer Prevention Institute of California, USA (U01 CA69417); University of Melbourne, Australia (U01 CA69638); Research Triangle Institute Informatics Support Center, USA (RFP No. N02PC45022-46). We would like to acknowledge the numerous volunteers for providing blood samples for the BCFR, the kConFab, the MBCSG, and the FCCC studies. For the kConFab study, we wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study and the many families who contribute to kConFab. The ABCFR was also supported by grants from the Victorian Health promotion Foundation, NHMRC, NSW Cancer Council, and the Victorian Breast Cancer Research Consortium (VBCRC). kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council [628333] and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. This work was also supported in part by the Eileen Stein-Jacoby Fund (to A.K.G.). A.K.G acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. M.C.S. is a NHMRC Senior Research Fellow and Victorian Breast Cancer Research Consortium Group Leader. S.L.E. is supported by a National Breast Cancer Foundation Australia (NBCF) Fellowship. A.B.S. is funded by an NHMRC Senior Research Fellowship. E.E.M.W. was supported by an NHMRC Dora Lush Postgraduate Student Scholarship. BRCA1 research in the Spurdle lab is supported by NHMRC project grant funding. J.L.H. is an Australia Fellow of the NHMRC and a VBCRC Group Leader. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating BCFR centers, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR.