Last update:
02-Nov-2000

Arch Hellen Med, 17(2), March-April 2000, 161-170

ORIGINAL PAPER

Development of a diagnostic method
for the detection of BRCA1 mutations
in breast/ovarian cancer families from Greece

I. KONSTANTOPOULOU,¹ Ch. KROUPIS,² A. LADOPOULOU,¹
A. PANTAZIDIS,¹ D. BOUMBA,¹ E.S. LIANIDOU,² M. PETERSEN,³
L. FLORENTIN,⁴ G. FOUNTZILAS,^5,6 D. YANNOUKAKOS^1
1Molecular Diagnostics Lab, I/R-RP, National Center for Scientific Research “Demokritos”, Athens
²Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens
³Department of Genetics, Institute of Child Health, Athens
⁴Molecular Biology and Cytogenetics Center “AlphaLab”, Athens
⁵AHEPA Hospital, Aristotle University of Thessaloniki, Medical School
⁶Hellenic Cooperative Oncology Group, Athens, Greece

OBJECTIVE The aim of this study was to design a diagnostic procedure for the detection and identification of BRCA1 gene mutation specific for Greek families at high risk for developing breast or ovarian cancer.
METHOD A combination of polymerase chain reaction, protein truncation test (for exon 11) and direct DNA sequencing techniques was applied on genomic DNA isolated from patients belonging to families with a history of two or more cases of breast cancer before 50 years or ovarian cancer at any age.
RESULTS Three frameshift-producing mutations were identified in exon 11, the 3741insA, the 1623del5-TTAAA and the 3099delT. The first mutation is reported only once in the BIC database, in a Turkish family living in Germany, the second is reported 6 times and the third is a novel mutation. The known polymorphisms from other populations, E1038G (exon 11), P871L (exon 11) and S1613G (exon 16), were also detected in the Greek population. One novel unclassified double variant was also detected in exon 16 (IVS16-68 G>A, IVS16-92 G>A) as well as another known unclassified intronic variant in intron 18 (IVS18+65 G>A).
CONCLUSIONS In this pilot study it was shown that (a) frameshift mutations of BRCA1 gene are identified in the Greek population, (b) known polymorphisms are found also in the Greek population, (c) this procedure can be used for diagnostic purposes in families with a history of breast and/or ovarian cancer.

Key words: BRCA1, Breast/ovarian cancer, Greece.