CHROMOSOME 11Q13 MARKERS AND D-TYPE CYCLINS IN BREAST-CANCER

One in six primary human breast cancers has DNA amplification centered on the cyclin D1 gene (CCND1) on chromosome 11q13. This genetic abnor mality is preferentially associated with estrogen-receptor positive tu mors and may define a sub-class of patients with an adverse prognosis. Although CCND1 has the credentials of a cellular oncogene, being a ta rget for chromosomal translocation and retroviral integration, the 11q 13 amplicon encompasses several other markers and CCND1 is not the onl y candidate for the key gene on the amplified DNA. To assess their rel ative importance, we have constructed a physical map of the amplified DNA and compared the extent and frequency of amplification across the region. Since it is likely that the gene providing the selective force for amplification will be expressed at elevated levels, we have also examined expression of both RNA and protein. By these criteria, cyclin D1 remains the strongest candidate for the key oncogene on the amplic on and we are currently investigating the functional consequences of i ts over-expression.