Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed.
BRCA1 and BRCA2 genes were screened for loss-of-function mutations in a series of 85 patients having at least one first- or second-degree relative affected by breast and/or ovarian cancer. All BRCA1 exons and BRCA2 exons 10 and 11 were screened with a combination of methods including SSCP, PTT and direct sequencing. We have found disease-associated mutations in 14 families (16.5%), eleven in BRCA1 and three in BRCA2. The known founder mutation 5382insC of BRCA1 was identified in seven unrelated families. The other mutations identified include the non-sense R1751X, the splice junction variant 5586G>A of BRCA1 and three frameshifts, 2024del5, 3034del4, and 6631del5, of BRCA2. Nine out of these 14 families had a family history of three or more breast/ovarian cancer cases. A large number of polymorphic or unclassified variants is also reported. Combined with our previously published data 5382insC was found in nine out of 20 families (45%), suggesting that this mutation may represent a common founder mutation in the Greek population.
Ladopoulou
A
A
Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research 'Demokritos', Ag. Paraskevi Attikis, 15310, Athens, Greece.
Kroupis
C
C
Konstantopoulou
I
I
Ioannidou-Mouzaka
L
L
Schofield
A C
AC
Pantazidis
A
A
Armaou
S
S
Tsiagas
I
I
Lianidou
E
E
Efstathiou
E
E
Tsionou
C
C
Panopoulos
C
C
Mihalatos
M
M
Nasioulas
G
G
Skarlos
D
D
Haites
N E
NE
Fountzilas
G
G
Pandis
N
N
Yannoukakos
D
D
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007124:Immunoenzyme Techniques; D007438:Introns; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011960:Receptors, Estrogen / Q000378:metabolism
D011960:Receptors, Estrogen