Recently, a novel candidate tumor suppressor gene, DPC 4/SMAD 4, has been implicated in the development of pancreatic cancers. Its location at human chromosome 18q21 prompted us to investigate this gene in a large series of primary tumors located outside the gastrointestinal tract which have been associated with loss of heterozygocity (LOH) at this locus. One hundred and thirty primary solid tumor samples (28 breast, 34 non-small cell lung, and 20 prostate cancers, and 40 osteosarcomas), 32 cell lines as well as 162 leukemia and lymphoma cases were analysed by Southern blotting and PCR-SSCP for deletions and mutations of the DPC 4 gene. In the breast cancer cell line MDA-MB-468, the gene was found to be homozygously deleted. Neither the primary solid tumor samples nor hematological malignancies had detectable abnormalities. Our study suggests that alterations of the DPC 4 gene, unlike in pancreatic cancer, are rare in breast, nonsmall cell lung and prostate cancers, osteosarcomas and hematopoietic malignancies.

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