DPC-4 SMAD-4 IN NONPANCREATIC TUMORS WITH FREQUENT LOH 18Q21 AND IN HEMATOLOGICAL MALIGNANCIES/

Recently, a novel candidate tumor suppressor gene, DPC 4/SMAD 4, has b een implicated in the development of pancreatic cancers. Its location at human chromosome 18q21 prompted us to investigate this gene in a la rge series of primary tumors located outside the gastrointestinal trac t 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 analy sed by Southern blotting and PCR-SSCP for deletions and mutations of t he 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 sam ples nor hematological malignancies had detectable abnormalities. Our study suggests that alterations of the DPC 4 gene, unlike in pancreati c cancer, are rare in breast, nonsmall cell lung and prostate cancers, osteosarcomas and hematopoietic malignancies.