Hereditary prostate cancer in Finland: Fine-mapping validates 3p26 as a major predisposition locus

Annika Rökman, Agnes B. Baffoe-Bonnie, Elizabeth Gillanders, Henna Fredriksson, Ville Autio, Tarja Ikonen, Kenneth D. Gibbs Jr, MaryPat Jones, Derek Gildea, Diane Freas-Lutz, Carol Markey, Mika P. Matikainen, Pasi A. Koivisto, Teuvo L.J. Tammela, Olli Kallioniemi, Jeffrey Trent, Joan E. Bailey-Wilson, Johanna Schleutker

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Abstract

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.
Original languageEnglish
Pages (from-to)43-50
JournalHuman Genetics
Volume116
Issue number1-2
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

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Finland
Prostatic Neoplasms
Genome
Contactins
Neural Cell Adhesion Molecule L1
Neoplasm Genes
Cell Adhesion Molecules
Microsatellite Repeats
Genetic Recombination
Population
Genes
Familial Prostate cancer
Mutation

Cite this

Rökman, A., Baffoe-Bonnie, A. B., Gillanders, E., Fredriksson, H., Autio, V., Ikonen, T., ... Schleutker, J. (2005). Hereditary prostate cancer in Finland: Fine-mapping validates 3p26 as a major predisposition locus. Human Genetics, 116(1-2), 43-50. https://doi.org/10.1007/s00439-004-1214-7
Rökman, Annika ; Baffoe-Bonnie, Agnes B. ; Gillanders, Elizabeth ; Fredriksson, Henna ; Autio, Ville ; Ikonen, Tarja ; Gibbs Jr, Kenneth D. ; Jones, MaryPat ; Gildea, Derek ; Freas-Lutz, Diane ; Markey, Carol ; Matikainen, Mika P. ; Koivisto, Pasi A. ; Tammela, Teuvo L.J. ; Kallioniemi, Olli ; Trent, Jeffrey ; Bailey-Wilson, Joan E. ; Schleutker, Johanna. / Hereditary prostate cancer in Finland : Fine-mapping validates 3p26 as a major predisposition locus. In: Human Genetics. 2005 ; Vol. 116, No. 1-2. pp. 43-50.
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title = "Hereditary prostate cancer in Finland: Fine-mapping validates 3p26 as a major predisposition locus",
abstract = "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.",
author = "Annika R{\"o}kman and Baffoe-Bonnie, {Agnes B.} and Elizabeth Gillanders and Henna Fredriksson and Ville Autio and Tarja Ikonen and {Gibbs Jr}, {Kenneth D.} and MaryPat Jones and Derek Gildea and Diane Freas-Lutz and Carol Markey and Matikainen, {Mika P.} and Koivisto, {Pasi A.} and Tammela, {Teuvo L.J.} and Olli Kallioniemi and Jeffrey Trent and Bailey-Wilson, {Joan E.} and Johanna Schleutker",
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Rökman, A, Baffoe-Bonnie, AB, Gillanders, E, Fredriksson, H, Autio, V, Ikonen, T, Gibbs Jr, KD, Jones, M, Gildea, D, Freas-Lutz, D, Markey, C, Matikainen, MP, Koivisto, PA, Tammela, TLJ, Kallioniemi, O, Trent, J, Bailey-Wilson, JE & Schleutker, J 2005, 'Hereditary prostate cancer in Finland: Fine-mapping validates 3p26 as a major predisposition locus', Human Genetics, vol. 116, no. 1-2, pp. 43-50. https://doi.org/10.1007/s00439-004-1214-7

Hereditary prostate cancer in Finland : Fine-mapping validates 3p26 as a major predisposition locus. / Rökman, Annika; Baffoe-Bonnie, Agnes B.; Gillanders, Elizabeth; Fredriksson, Henna; Autio, Ville; Ikonen, Tarja; Gibbs Jr, Kenneth D. ; Jones, MaryPat; Gildea, Derek; Freas-Lutz, Diane; Markey, Carol; Matikainen, Mika P.; Koivisto, Pasi A.; Tammela, Teuvo L.J.; Kallioniemi, Olli; Trent, Jeffrey; Bailey-Wilson, Joan E.; Schleutker, Johanna.

In: Human Genetics, Vol. 116, No. 1-2, 2005, p. 43-50.

Research output: Contribution to journalArticleScientificpeer-review

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

VL - 116

SP - 43

EP - 50

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 1-2

ER -

Rökman A, Baffoe-Bonnie AB, Gillanders E, Fredriksson H, Autio V, Ikonen T et al. Hereditary prostate cancer in Finland: Fine-mapping validates 3p26 as a major predisposition locus. Human Genetics. 2005;116(1-2):43-50. https://doi.org/10.1007/s00439-004-1214-7