DNA AMPLIFICATIONS 20Q13 AND MDM2 DEFINE DISTINCT SUBSETS OF EVOLVED BREAST AND OVARIAN-TUMORS

DNA amplification seems to be particularly frequently in human breast tumours and has been associated with cancer evolution and aggressivene ss. Recent data indicate that new events should be added to the list, such as the amplifications at chromosome 20q13 or the MDM2 gene. The p resent work aimed at determining the incidence and clinicopathological signification of these amplifications in a large series of breast and ovarian tumours. We tested 1371 breast and 179 ovarian tumours by Sou thern blotting and observed amplification of 20q13 in 5.4% breast and 2.8% ovarian tumours, whereas MDM2 was found amplified in 5.3% and 3.8 % of breast and ovarian tumours respectively. MDM2 RNA expression leve ls were analysed in a subset of 57 breast tumours and overexpression w as observed in 4/57 (17%) of the tumours. Elevated expression levels c oincided with amplification of the gene. In breast cancer, 20q13 and M DM2 amplifications seem to define subsets of aggressive tumours. Indee d, 20q13 was correlated to axillary nodal involvement and occurred pre ferentially in younger patients (< 50 years). Furthermore, 20q13 corre lated, as did MDM2 amplification to aneuploidy. In parallel, we had al so tested our tumour DNAs for amplification of CCND1. ERBB-2 and MYC, which made it possible to test for correlations with 20q13 or MDM2 amp lifications. Whereas 20q13 showed a very strong correlation to CCD1 am plifications that of MDM2 was prevalent in MYC-amplified tumours. Inte restingly, 20q13 and MDM2 amplifications showed some degree of correla tion to each other, which may possibly be owing to the fact that both events occurred preferentially in aneupliod tumours. In ovarian cancer , no statistically significantly correlation was observed. However, 20 q13 amplification occurred preferentially in stage 3 tumours and MDM2 was correlated to ERBB-2 amplification. This may suggest that in ovari an tumours also, 20q13 and MDM2 amplifications occur in late or aggres sive cancers.