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Structural changes of the human retinoblastoma gene have been demonstrated previously in retinoblastoma and some clinically related tumors including osteosarcoma. Structural aberrations of the retinoblastoma locus (RB1) were observed in 25% of breast tumor cell lines studied and 7% of the primary tumors. These changes include homozygous internal deletions and total deletion of RB1; a duplication of an exon was observed in one of the cell lines. In all cases, structural changes either resulted in the absence or truncation of the RB1 transcript. No obvious defect in RB1 was detected by DNA blot analysis in primary tumors or cell lines from Wilms' tumor, cervical carcinoma, or hepatoma. These results further support the concept that the human RB1 gene has pleiotropic effects on specific types of cancer.

The aim of the present study was to identify genes whose expression and/or organisation are altered in the diseased breast, as compared to the normal breast. Alteration of one or more genes examined has been found to occur in over 60% of breast tumour samples. Changes to three cellular proto-oncogenes are frequent, and amplification of two of these genes correlates with poor short-term prognosis. Deletion of RB-1 a tumour suppressor gene, has been detected and although these deletions do not correlate with poor prognosis, they occur more commonly in advanced tumours. A loss of sequences encoding the progesterone receptors has also been found to be frequent.

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