Loss of heterozygosity in bilateral breast cancer.
Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age < 50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.
Kollias
J
J
Nottingham City Hospital, UK. jkollias@mail.rah.sa.gov.au
Man
S
S
Marafie
M
M
Carpenter
K
K
Pinder
S
S
Ellis
I O
IO
Blamey
R W
RW
Cross
G
G
Brook
J D
JD
D000328:Adult; D017668:Age of Onset; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors