TY - JOUR
T1 - Hereditary prostate cancer in Finland
T2 - Fine-mapping validates 3p26 as a major predisposition locus
AU - Rökman, Annika
AU - Baffoe-Bonnie, Agnes B.
AU - Gillanders, Elizabeth
AU - Fredriksson, Henna
AU - Autio, Ville
AU - Ikonen, Tarja
AU - Gibbs Jr, Kenneth D.
AU - Jones, MaryPat
AU - Gildea, Derek
AU - Freas-Lutz, Diane
AU - Markey, Carol
AU - Matikainen, Mika P.
AU - Koivisto, Pasi A.
AU - Tammela, Teuvo L.J.
AU - Kallioniemi, Olli
AU - Trent, Jeffrey
AU - Bailey-Wilson, Joan E.
AU - Schleutker, Johanna
PY - 2005
Y1 - 2005
N2 - In a recent genome-wide linkage (GWL) analysis of Finnish families at
high risk for prostate cancer, we found two novel putative
susceptibility loci at 3p25-p26 and 11q14. Here, we report the
fine-mapping of these two critical regions at high resolution with 39
microsatellite markers in 16 families, including multiplex families that
were not used in the GWL scan. The maximum multipoint HLOD was 3.39 at
3p26 and 1.42 at 11q14. The highest LOD scores were seen around markers
D3S1270 and D3S4559 (α=0.89), covering approximately two megabases. The
two known genes in this region CHL1 (cell adhesion molecule with homology to L1CAM) and CNTN6 (contactin 6)
were screened for exonic mutations in the families showing the
strongest linkage, but no disease-segregating sequence variants were
observed. The recombination map pointed to a region proximal to the area
of best linkage, suggesting that more genes may need to be investigated
as candidates. These results provide strong evidence for the existence
of a prostate cancer susceptibility gene at 3p26 in Finnish prostate
cancer families. This locus has not been strongly linked with hereditary
prostate cancer in other populations. However, the mildly positive 3p
LOD scores in a recent GWL analysis of patients from the United States
suggest that the locus may also be important in other populations.
AB - In a recent genome-wide linkage (GWL) analysis of Finnish families at
high risk for prostate cancer, we found two novel putative
susceptibility loci at 3p25-p26 and 11q14. Here, we report the
fine-mapping of these two critical regions at high resolution with 39
microsatellite markers in 16 families, including multiplex families that
were not used in the GWL scan. The maximum multipoint HLOD was 3.39 at
3p26 and 1.42 at 11q14. The highest LOD scores were seen around markers
D3S1270 and D3S4559 (α=0.89), covering approximately two megabases. The
two known genes in this region CHL1 (cell adhesion molecule with homology to L1CAM) and CNTN6 (contactin 6)
were screened for exonic mutations in the families showing the
strongest linkage, but no disease-segregating sequence variants were
observed. The recombination map pointed to a region proximal to the area
of best linkage, suggesting that more genes may need to be investigated
as candidates. These results provide strong evidence for the existence
of a prostate cancer susceptibility gene at 3p26 in Finnish prostate
cancer families. This locus has not been strongly linked with hereditary
prostate cancer in other populations. However, the mildly positive 3p
LOD scores in a recent GWL analysis of patients from the United States
suggest that the locus may also be important in other populations.
U2 - 10.1007/s00439-004-1214-7
DO - 10.1007/s00439-004-1214-7
M3 - Article
SN - 0340-6717
VL - 116
SP - 43
EP - 50
JO - Human Genetics
JF - Human Genetics
IS - 1-2
ER -
