LOCALIZATION OF SMAD5 AND ITS EVALUATION AS A CANDIDATE MYELOID TUMOR-SUPPRESSOR

Acquired interstitial or complete losses of chromosome 5 are recurring anomalies associated with preleukemic myelodysplasia and acute myelog enous leukemia with a poor prognosis. Previous studies have delineated a potential myeloid tumor suppressor locus to a <2.4-Mb interval betw een the genes for IL9 and EGR1 on 5q31. In this report, we have locali zed the SMAD5 gene, a homologue of the tumor suppressor genes SMAD4/DP C-4 and SMAD2/JV18.1, to the minimal myeloid tumor suppressor locus an d characterized its open reading frame and genomic organization. SMAD5 transcripts are readily detectable in hematolymphoid tissues and leuk emic blasts. Absence of intragenic mutations in the remaining SMAD5 al lele of leukemic patients and multiple solid tumor cell lines prescree ned for loss of heterozygosity suggests that SMAD5 may not be a common target of somatic inactivation in malignancy.