Human Molecular Genetics Advance Access originally published online on May 3, 2007
Human Molecular Genetics 2007 16(11):1271-1278; 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, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108, 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, 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 and Tampere University Hospital, University of Tampere, Tampere, Finland, 30 University of Ulm ICPCG group, 31 Department of Urology, 32 Institute of Human Genetics, University of Ulm, Germany, 33 University of Umeå ICPCG group, 34 Oncologic Centre, Umeå University, Umeå, Sweden and 35 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
* To whom correspondence should be addressed. Tel: +1 8015879351; Fax: +1 8015816052; Email: nicola.camp{at}utah.edu
Received January 28, 2007; Accepted March 20, 2007
Previously, an analysis of 14 extended, high-risk Utah pedigrees localized in the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.1 (flanked on each side by three recombinants) contained 31 annotated genes. In this large, multi-centered, collaborative study, we performed statistical recombinant mapping in 54 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 1213 such that each pedigree was required to contain both 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 down 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 11 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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