Fine mapping of familial prostate cancer families narrows the interval for a susceptibility locus on chromosome 22q12.3 to 1.36 Mb
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Genetic studies suggest that hereditary prostate cancer is a genetically heterogeneous disease with multiple contributing loci. Studies of high-risk prostate cancer families selected for aggressive disease, analysis of large multigenerational families, and a meta-analysis from the International Consortium for Prostate Cancer Genetics (ICPCG), all highlight chromosome 22q12.3 as a susceptibility locus with strong statistical significance. Recently, two publications have narrowed the 22q12.3 locus to a 2.18 Mb interval using 54 high-risk families from the ICPCG collaboration, as defined by three recombination events on either side of the locus. In this paper, we present the results from fine mapping studies at 22q12.3 using both haplotype and recombination data from 42 high-risk families contributed from the Mayo Clinic and the Prostate Cancer Genetic Research Study (PROGRESS) mapping studies. No clear consensus interval is present when all families are used. However, in the subset of 14 families with ≥5 affected men per family, a 2.53-Mb shared consensus segment that overlaps with the previously published interval is identified. Combining these results with data from the earlier ICPCG study reduces the three-recombination interval at 22q12.3 to approximately 1.36 Mb.
This research was supported by grants from the National Institutes of Health R01 CA80122 (JLS), RO1 CA78836 (EAO), RO1 CA089600, and RO1 CA72818 (SNT and DS), with additional support from the Prostate Cancer Foundation, the Fred Hutchinson Cancer Research Center, the Intramural Program of the National Human Genome Research Institute and the Center for Inherited Disease Research. We are grateful for the continued participation of PROGRESS and Mayo family members in this research.
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