Abstract for presentation at 11th International Congress of Human Genetics

Worldwide investigation of a BRCA1 founder mutation causing breast-ovarian cancer found exclusively in the Greek population

  • Dr Theodore Anagnostopoulos, Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research, Greece
  • Dr Irene Konstantopoulou, Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research, Greece
  • Dr George Nasioulas, Molecular Biology Department, Diagnostic and Therapeutic Center of Athens HYGEIA, Athens, Greece
  • Dr Alex Dobrovic, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia
  • Dr Mary-Anne Young, Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Australia
  • Dr Gillian Mitchell, Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Australia
  • Dr George Fountzilas, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • Dr Drakoulis Yannoukakos, Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research, Greece

    • We have performed population screening in 200 breast/ovarian cancer families in Greece which has revealed that approximately 20% (9/49) of all carriers of a deleterious mutation in BRCA1 and BRCA2 genes, contain the base substitution G to A at position 5331 of BRCA1 gene. This generates the amino acid change G1738R for which based on a combination of genetic, in silico and histopathological analysis there are strong suggestions that it is a causative mutation. The same base change has only been detected in four additional Greek breast cancer families worldwide: two in Australia, one in the US and one in Southern Italy.
    In order to explain the prevalence of this mutation exclusively in the Greek population, its genealogical history was examined. Analysis of flanking intragenic SNPs in the 13 reference individuals from all families worldwide showed identical haplotypes matching one of the common haplotypes observed in all BRCA1 carriers. Additional extragenic microsatellite markers analysis and comparison with control individuals, suggested a common origin for the mutation.
    The mutation was then analysed further using a recently developed Bayesian approach that reconstructs the geneaology of the gene investigated while providing minimum estimates for the age of the mutation inherited by the members of coherent trees.
    Considering the large degree of genetic heterogeneity in the Greek population, the identification of a frequent founder mutation greatly facilitates genetic screening.

    Conference Organiser - ICMS Pty Ltd