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, MaryPat Jones, Derek Gildea, Diane Freas-Lutz, Carol Markey, Mika P. Matikainen, Pasi A. Koivisto, Teuvo L J Tammela, Olli P. Kallioniemi, Jeffrey Trent, Joan E. Bailey-Wilson, Johanna Schleutker

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)43-50
Number of pages8
JournalHuman Genetics
Volume116
Issue number1-2
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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

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, Kenneth D.; Jones, MaryPat; Gildea, Derek; Freas-Lutz, Diane; Markey, Carol; Matikainen, Mika P.; Koivisto, Pasi A.; Tammela, Teuvo L J; Kallioniemi, Olli P.; Trent, Jeffrey; Bailey-Wilson, Joan E.; Schleutker, Johanna.

In: Human Genetics, Vol. 116, No. 1-2, 01.2005, p. 43-50.

Research output: Contribution to journalArticle

Rökman, A, Baffoe-Bonnie, AB, Gillanders, E, Fredriksson, H, Autio, V, Ikonen, T, Gibbs, KD, Jones, M, Gildea, D, Freas-Lutz, D, Markey, C, Matikainen, MP, Koivisto, PA, Tammela, TLJ, Kallioniemi, OP, 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
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 Jan;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, Kenneth D. ; Jones, MaryPat ; Gildea, Derek ; Freas-Lutz, Diane ; Markey, Carol ; Matikainen, Mika P. ; Koivisto, Pasi A. ; Tammela, Teuvo L J ; Kallioniemi, Olli P. ; 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.
@article{9aa0ef18efe24c09b3f51ab7af1aff04,
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, {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 Kallioniemi, {Olli P.} and Jeffrey Trent and Bailey-Wilson, {Joan E.} and Johanna Schleutker",
year = "2005",
month = "1",
doi = "10.1007/s00439-004-1214-7",
language = "English (US)",
volume = "116",
pages = "43--50",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "1-2",

}

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, 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 P.

AU - Trent, Jeffrey

AU - Bailey-Wilson, Joan E.

AU - Schleutker, Johanna

PY - 2005/1

Y1 - 2005/1

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.

UR - http://www.scopus.com/inward/record.url?scp=19944426207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944426207&partnerID=8YFLogxK

U2 - 10.1007/s00439-004-1214-7

DO - 10.1007/s00439-004-1214-7

M3 - Article

C2 - 15549392

AN - SCOPUS:19944426207

VL - 116

SP - 43

EP - 50

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 1-2

ER -