Absence of CCND1 gene amplification in breast tumours of BRCA1 mutation carriers.
OBJECTIVE
It was recently reported that significantly fewer breast tumours of BRCA1 mutation carriers overexpressed cyclin D1 and HER2 protein than tumours of age matched breast cancer cases unselected for family history. This study aimed to examine the genetic basis of this reduction by determining the frequency of tumours within this cohort showing DNA amplification of these genes.


METHODS
Paraffin wax embedded sections of breast tumours from BRCA1 mutation carriers and age, grade, histological type, and tumour size matched non-familial controls that had previously been stained for cyclin D1 and HER2 protein overexpression were analysed for CCND1 and HER2 gene amplification using fluorescence in situ hybridisation.


RESULTS
CCND1 amplification was detected in none of the 30 tumours of the BRCA1 mutation carriers and in 19 of 74 tumours of the matched controls. Of those samples previously determined to overexpress the HER2 protein, HER2 amplification was detected in one of three tumours from BRCA1 mutation carriers and in 13 of 17 tumours of the age matched non-familial cases.


CONCLUSIONS
None of the tumours of BRCA1 mutation carriers showed CCND1 amplification and only one tumour showed HER2 amplification. In contrast, a large proportion of cyclin D1 and HER2 overexpression in tumours of non-familial breast cancer cases could be accounted for by amplification of these genes. These data suggest that breast tumorigenesis in BRCA1 mutation carriers occurs by a molecular mechanism distinct from that of age matched non-familial cases.
Vaziri
S A
SA
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Tubbs
R R
RR
Darlington
G
G
Casey
G
G
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D019398:Genes, BRCA1; D018734:Genes, erbB-2; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation
D019938:Cyclin D1