Τίτλος:
Identification of germline BRCA1 and BRCA2 genetic alterations in Greek
breast cancer moderate-risk and low-risk individuals - correlation with
clinicopathological data
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The current study was designed to evaluate the prevalence of BRCA1 and
BRCA2 germline mutations in Greek moderate- and low-risk individuals
with respect to clinicopathological phenotype and clinical outcome of
breast cancer. Ninety-four consecutive individuals were prospectively
recruited from two University Breast Cancer Clinics (Hippokrateion
Hospitan and Laikon Hospital) between 1989 and 1999 and were categorized
as moderate-risk and low-risk individuals for carrying BRCA1/2 germline
mutations. To identify the underlying mutations, protein-truncation test
and single-strand conformation polymorphism methods were used, followed
by direct sequencing. Three novel BRCA1 missense mutations, one novel
BRCA1 intronic deletion, three novel (previously reported) BRCA2
truncating mutations, and one novel BRCA2 missense mutation were
identified in the moderate-risk group of individuals studied. The
BRCA1/2 missense mutations as well as the single intronic variant
identified were designated as unclassified genetic variants. Two BRCA1
unclassified genetic variants (missense mutations) were detected in two
of the three (66.7%) male breast cancer patients analyzed, while the
third one was identified in a sporadic (low-risk) breast cancer patient.
Clinicopathological characteristics of breast carcinomas originating
from BRCA1/2 heterozygotes were consistent with those already reported
and not different from those observed in BRCA1/2 mutation (-) breast
cancer patients. Furthermore, BRCA1/2 mutation carriers presented an
excellent 4.5-year overall survival (100%). Our results reveal the
unique characteristics of BRCA1/2 mutation status, genotype-phenotype
correlations, and prognosis, in moderate- and low-risk individuals of
Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2 genes
appears to be a heterogeneous syndrome in the Greek population.
Συγγραφείς:
Kataki, A
Gomatos, IP
Pararas, N
Armakolas, A and
Panousopoulos, D
Karantzikos, G
Voros, D
Zografos, G and
Markopoulos, C
Leandros, E
Konstadoulakis, MM
Περιοδικό:
Application of Clinical Genetics
Λέξεις-κλειδιά:
BRCA1; BRCA2; breast cancer; low risk; moderate risk; mutations
DOI:
10.1111/j.1399-0004.2004.00400.x
