Human Molecular Genetics Advance Access published online on May 3, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm075
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Compelling Evidence for a Prostate Cancer Gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics
1 University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA 2 African American Hereditary Prostate Cancer ICPCG Group 3 Fox Chase Cancer Center, Philadelphia, PA, USA 4 National Human Genome Research Institute, NIH, Bethesda, MD, USA 5 Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 6 Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, AZ, USA 7 ACTANE consortium ICPCG Group 8 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia 9 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia 10 Department of Oncology, McGill University, Montreal, Quebec, Canada 11 The Norwegian Radium Hospital, Oslo, Norway 12 Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK 13 Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK 14 Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA 15 BC/CA/HI ICPCG Group 16 Department of Health Research and Policy, Stanford School of Medicine, CA, USA 17 Stanford Comprehensive Cancer Center, Stanford School of Medicine, CA, USA 18 Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, CA, USA 19 Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA 20 FHCRC ICPCG Group 21 Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, WA, USA 22 Cancer Genetics Branch, National Institutes of Health, Bethesda, MD, USA 23 Institute for Systems Biology, Seattle, WA, USA 24 Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA 25 Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, MN, USA 26 University of Michigan ICPCG Group 27 Department of Genetics, University of North Carolina, Chapel Hill, NC, USA 28 University of Michigan, Ann Arbor, MI, USA 29 University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland 30 University of Ulm ICPCG Group 31 Dept of Urology, University of Ulm, Germany 32 Institute of Human Genetics, University of Ulm, Germany 33 University of Umeå ICPCG Group 34 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 35 Oncologic Centre, Umeå University, Umeå, Sweden
Corresponding author: Nicola J. Camp, Ph.D., Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108. Phone (801) 587-9351, Fax (801) 581-6052, Email: nicola.camp{at}utah.edu
Received January 28, 2007; Revised March 20, 2007; Accepted March 20, 2007
Previously, an analysis of 14 extended, high-risk Utah pedigrees localized the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.1 (flanked on each side by three recombinants), which contained 31 annotated genes. In this large, multi-centered, collaborative study, we performed statistical recombinant mapping in fifty-four pedigrees selected to be informative for recombinant mapping from nine member groups of the International Consortium for Prostate Cancer Genetics (ICPCG). These 54 pedigrees included the 14 extended pedigrees from Utah and 40 pedigrees from eight other ICPCG member groups. The additional 40 pedigrees were selected from a total pool of 1,213 such that each pedigree was required to both contain at least four prostate cancer (PRCA) cases and exhibit evidence for linkage to the chromosome 22q region. The recombinant events in these 40 independent pedigrees confirmed the previously proposed region. Further, when all 54 pedigrees were considered, the three-recombinant consensus region was narrowed by more than a megabase to 2.2 Mb at chromosome 22q12.3 flanked by D22S281 and D22S683. This narrower region eliminated 20 annotated genes from that previously proposed, leaving only eleven genes. This region at 22q12.3 is the most consistently identified and smallest linkage region for PRCA. This collaborative study by the ICPCG illustrates the value of consortium efforts and the continued utility of linkage analysis using informative pedigrees to localize genes for complex diseases.
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