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RNASEL mutations in hereditary prostate cancer
  1. H Chen1,
  2. A R Griffin1,
  3. Y-Q Wu1,
  4. L P Tomsho1,
  5. K A Zuhlke1,
  6. E M Lange5,
  7. S B Gruber1,3,
  8. K A Cooney1,2,4
  1. 1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
  2. 2Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA
  3. 3Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
  4. 4Ann Arbor Department of Veteran’s Affairs, Ann Arbor, MI, USA
  5. 5Section of Biostatistics, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  1. Correspondence to:
 Dr K A Cooney, 7310 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0946, USA; 
 kcooney{at}umich.edu

https://doi.org/10.1136/jmg.40.3.e21

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    Prostate cancer linkage to a broad region on chromosome 1q24-25 was first described by Smith et al1 in 1996. In this initial report, analysis of 91 multiplex prostate cancer families from North America and Sweden showed significant evidence for prostate cancer linkage surrounding marker D1S158 with a peak multipoint lod score assuming heterogeneity of 5.43 at marker D1S422. Although approximately one-third of prostate cancer families were estimated to be linked to this locus in this first set of families, additional studies suggest that the percentage of families with prostate cancer attributable to mutations in HPC1 may be significantly less (<5%).2

    Recently, Carpten et al3 provided evidence that the RNASEL gene may be a candidate gene for HPC1. This gene is in the previously described 1q linkage peak, and deleterious mutations were identified in two of eight families with evidence for linkage to 1q24-25 markers. Additional functional data in support of the hypothesis that RNASEL mutations contribute to hereditary prostate cancer include: (1) evidence of loss of heterozygosity (LOH) of the wild type allele in prostate cancer from a patient harbouring a germline truncating mutation (E265X), and (2) absent RNASEL expression in prostate cancer tissue from a patient with the E265X mutation.

    The University of Michigan Prostate Cancer Genetics Project (PCGP) was established in 1995 with the major goal of characterising the molecular basis of prostate cancer susceptibility. Fifty-nine families from the PCGP were used in the first confirmatory report of prostate cancer linkage to chromosome 1q24-25 markers.4 In this present report, we set out to determine the contribution of RNASEL mutations to prostate cancer susceptibility in a set of PCGP families.

    MATERIAL AND METHODS

    Patient selection

    Men with prostate cancer selected for this study are participants in the University of Michigan PCGP. Current enrolment criteria for this family based study …

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