CYCLIN GENE AMPLIFICATION AND OVEREXPRESSION IN BREAST AND OVARIAN CANCERS - EVIDENCE FOR THE SELECTION OF CYCLIN D1 IN BREAST AND CYCLIN-EIN OVARIAN-TUMORS

Evidence of the involvement of cyclin genes in genetic alterations in human cancer is growing. In the present study, we investigated the amp lification, in human breast and ovarian cancer, of 5 cyclin genes; cyc lin A, cyclin D1, cyclin D2, cyclin D3 and cyclin E. For this purpose, a series of 1,171 breast and 237 ovarian tumors tested for DNA amplif ication by Southern blotting and a subset of 132 breast and 22 ovarian cancers were analyzed for RNA expression levels by slot-blot and Nort hern blotting. In breast tumors, only cyclin DI was found to be activa ted in a sizeable fraction of the tumors (amplification 12.6%, overexp ression 19%). Cyclin A, D2, D3, and E genes never, or only on rare occ asions, showed increased DNA copy numbers and were never found overexp ressed at the RNA level. Amplification of cyclin D1 correlated with ER (+) breast cancer and the presence of lymph-node metastasis. Interesti ngly, we were also able to determine an association with invasive lobu lar carcinoma. Our data suggest that cyclin D1 activation determines t he evolution of a particular subset of estrogen-responsive tumors. Dat a obtained in ovarian tumors contrasted with observations in breast ca ncer. Cyclin D1 DNA amplification was much less frequent in ovarian th an in breast tumors (3.3% vs. 12.6%), whereas cyclin E amplification a nd overexpression were observed in a significant number of cases (12.5 % and 18.0% respectively). Cyclin A, cyclin D2 and D3 rarely showed an omalies at the DNA level and were never overexpressed. No clear correl ation could be observed between amplification of the cyclin E gene and tumor type, stage or grade in ovarian cancer. Data presented here sug gest distinct pathways of cyclin activation in human breast and ovaria n cancer. (C) 1996 Wiley-Liss, Inc.