Profile of genetic alterations and tumorigenicity of human breast cancer cells

The profile of genetic alterations in four breast carcinoma cell lines, SK- BR-3, BT-474, MDA-MB361 and ZR-75-1 was examined by comparative genomic hyb ridization, G-band karyotyping, reverse chromosome painting and fluorescenc e in situ hybridization of single-copy genes. These lines are aneuploid wit h complex structural rearrangements and have DNA copy-number imbalances inv olving multiple sites that include amplification of ERBB-2 and MYC protoonc ogenes which are implicated in breast cancer pathogenesis. A novel site of high level amplification was mapped on chromosome 15. All lines were tumori genic in nude mice, however, the latency and the incidence of tumor formati on varied; SK-BR-3 and MDA-MB361 produced tumors in a shorter time and had a higher total number of genomic imbalances compared to BT-474 and ZR-75-1 cells. Tumor cell behavior in vivo was not reflected by the rate of in vitr o cell proliferation. Underrepresentation on the long arm of chromosome 18 was the sole alteration that correlated with an increased tumorigenicity. C hromosome 18q is rich in tumor suppressor genes and its loss is prevalent i n. primary node-positive breast tumors. Cell lines with monoclonal populati ons preserve the genetic characteristics of the primary tumor and their use may facilitate the detection of specific alterations associated with breas t cancer progression.