Mutations of the E2F4 gene in hematological malignancies having microsatellite instability

Mutations of coding repeats within the E2F4, TGF-beta RII, BAX, IGFIIR, and hMSH3 are critical targets of microsatellite instability (MSI) in many kin ds of cancers. We analyzed 9 childhood acute lymphoblastic leukemia (ALL) s amples, 5 acute myelocytic leukemia (AML) samples, and 10 adult T-cell leuk emia (ATL) samples having MSI to determine whether they had mutations of th e E2F4, TGF-beta RII, BAX, IGFIIR, and hMSH3 genes. Frameshift mutations we re found at trinucleotide repeats within a coding exon of the E2F4 gene in 2 of 10 (20%) ATL samples and 1 of 9 (11%) childhood ALL samples. No mutati ons were found in the TGF-beta RII, BAX, IGFIIR, and hMSH3 genes. E2F4 is a transcription factor that influences the cell-cycle progression. These res ults suggest that mutations of the E2F4 gene, presumably caused by an abnor mality of one of the DNA repair genes, may play an important role in develo pment of ATL and childhood ALL. (C) 2000 by The American Society of Hematol ogy.