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Familial Cancer

, 8:473 | Cite as

Haplotypes of the I157T CHEK2 germline mutation in ethnically diverse populations

  • Bella Kaufman
  • Yael Laitman
  • Jacek Gronwald
  • Robert Winqvist
  • Arvids Irmejs
  • Jan Lubinski
  • Katri Pylkäs
  • Janis Gardovskis
  • Edvins Miklasevics
  • Eitan FriedmanEmail author
Article

Abstract

The CHEK2*I157T missense mutation, reported in ethnically diverse, high-risk families, moderately increases breast and colon cancer risk. The present study assessed whether this mutation represents a founder mutation. Participants identified in high risk clinics or from consecutive cancer patients in Israel, Poland, Latvia, and Finland, were either carriers of the CHEK2*I157T mutation or non-carrier family members. Multi-locus genotyping employed two intragenic markers and five CHEK2 gene flanking markers, spanning about 645 kb. Haplotyping was done when families were available for phasing. Overall, 101 individuals (83 I157T*CHEK2 mutation carriers) were genotyped: 16 Finnish individuals from 11 families (14 mutation carriers, two non-carrier family members), 50 Polish individuals (20 families) (35 carriers, 15 non-carriers), 28 unrelated Latvian mutation carriers, and seven Israeli participants (two families) (six mutation carriers, one non-carrier). Overall 36/83 mutation carriers (43%) were diagnosed with breast cancer, 15/83 (18%)—colon cancer, three—ovarian cancer, one—thyroid cancer, and the rest (n = 28) were asymptomatic. A common core haplotype was detected in all I157T*CHEK2 mutation carriers of Israeli, Polish, and Finnish origin between markers D22S275-D22S689 (~258 kb), with a different allele pattern in Latvians. In conclusion, CHEK2*I157T missense mutation is a founder mutation in ethnically diverse populations, but may also be a mutational hotspot.

Keywords

CHEK2 gene Founder mutation Germline mutations Haplotype High risk cancer families 

Notes

Acknowledgement

This grant was partially funded by a grant from the Tel-Aviv University to Eitan Friedman

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Bella Kaufman
    • 1
  • Yael Laitman
    • 2
  • Jacek Gronwald
    • 4
  • Robert Winqvist
    • 5
  • Arvids Irmejs
    • 6
  • Jan Lubinski
    • 4
  • Katri Pylkäs
    • 5
  • Janis Gardovskis
    • 6
  • Edvins Miklasevics
    • 6
  • Eitan Friedman
    • 2
    • 3
    Email author
  1. 1.Institute of OncologyChaim Sheba Medical CenterTel-HashomerIsrael
  2. 2.The Susanne Levy Gertner Oncogenetics UnitThe Danek Gertner Institute of Human Genetics, Chaim Sheba Medical CenterTel-HashomerIsrael
  3. 3.Sackler Faculty of MedicineTel Aviv UniversityRamat AvivIsrael
  4. 4.Department of Genetics and PathologyInternational Hereditary Cancer Center, Pomeranian Medical UniversitySzczecinPoland
  5. 5.Laboratory of Cancer Genetics, Biocenter OuluOulu University Hospital, University of OuluOuluFinland
  6. 6.Hereditary Cancer InstituteRiga Stradins UniversityRigaLatvia

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