BRCA2 mutations in primary breast and ovarian cancers.
The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1.
Lancaster
J M
JM
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Wooster
R
R
Mangion
J
J
Phelan
C M
CM
Cochran
C
C
Gumbs
C
C
Seal
S
S
Barfoot
R
R
Collins
N
N
Bignell
G
G
Patel
S
S
Hamoudi
R
R
Larsson
C
C
Wiseman
R W
RW
Berchuck
A
A
Iglehart
J D
JD
Marks
J R
JR
Ashworth
A
A
Stratton
M R
MR
Futreal
P A
PA
D000368:Aged; D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D017931:DNA Primers; D005819:Genetic Markers; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors