MUTATIONAL ANALYSIS OF THE TUMOR-SUPPRESSOR SMAD2 IN ACUTE LYMPHOID AND MYELOID-LEUKEMIA

Smad4 is a tumor suppressor that is inactivated in about 50% of pancre atic carcinomas. Mutations in this gene have also been found with vari able, yet much lower frequency in other tumor types and were absent fr om a large number of samples from patients with hematological malignan cies. Smad2 shows considerable sequence similarity with Smad4 and coop erates with it in the growth inhibitory TGF-beta pathway. Smad2 mutati ons have been found in a fraction of colon carcinomas and have been sh own to impair the function of the corresponding proteins. However, onl y a few other tumor types have been screened for Smad2 mutations so fa r. Therefore, we analyzed 50 primary tumor samples from patients with acute lymphoid or myeloid leukemia (ALL or AML) and five cell lines of hematopoietic origin for alterations in the Smad2 gene. None of the s pecimens tested carried mutations in the conserved MH1 or MH2 domains of Smad2.