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 pancreatic carcinomas. Mutations in this gene have also been found with variable, yet much lower frequency in other tumor types and were absent from a large number of samples from patients with hematological malignancies. Smad2 shows considerable sequence similarity with Smad4 and cooperates with it in the growth inhibitory TGF-beta pathway. Smad2 mutations have been found in a fraction of colon carcinomas and have been shown to impair the function of the corresponding proteins. However, only a few other tumor types have been screened for Smad2 mutations so far. 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 specimens tested carried mutations in the conserved MH1 or MH2 domains of Smad2.
Institut für Medizinische Biologie, Wien, Austria.
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Wieser
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Gruber
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Rieder
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Fonatsch
D001483:Base Sequence; D001854:Bone Marrow Cells; D002887:Chromosomes, Human, Pair 18; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood / Q000235:genetics*; D007947:Leukemia, Megakaryoblastic, Acute / Q000097:blood / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D051899:Smad2 Protein; D015534:Trans-Activators; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D015534:Trans-Activators