Absence of CCND 1 gene amplification in breast tumours of BRCA1 mutation carriers

Background/Aims It was recently reported that significantly fewer breast tu mours of BRCA1 mutation carriers overexpressed cyclin D1 and HER2 protein t han tumours of age matched breast cancer cases unselected for family histor y. This study aimed to examine the genetic basis of this reduction by deter mining the frequency of tumours within this cohort showing DNA amplificatio n of these genes. Methods-Paraffin wax embedded sections of breast tumours from BRCA1 mutatio n carriers and age, grade, histological type, and tumour size matched non-f amilial controls that had previously been stained for cyclin D1 and HER2 pr otein overexpression were analysed for CCND1 and HER2 gene amplification us ing fluorescence in situ hybridisation. Results-CCND1 amplification was detected in none of the 30 tumours of the B RCA1 mutation carriers and in 19 of 74 tumours of the matched controls. Of those samples previously determined to overexpress the HER2 protein, HER2 a mplification was detected in one of three tumours from BRCA1 mutation carri ers and in 13 of 17 tumours of the age matched nonfamilial cases. Conclusion-None of the tumours of BRCA1 mutation carriers showed CCND1 ampl ification and only one tumour showed HER2 amplification. In contrast, a lar ge proportion of cyclin D1 and HER2 overexpression in tumours of non-famili al breast cancer cases could be accounted for by amplification of these gen es. These data suggest that breast tumorigenesis in BRCA1 mutation carriers occurs by a molecular mechanism distinct from that of age matched non-fami lial cases.