title: Mutations of the E2F4 gene in hematological malignancies having microsatellite instability.
abstract: Mutations of coding repeats within the E2F4, TGF-betaRII, BAX, IGFIIR, and hMSH3 are critical targets of microsatellite instability (MSI) in many kinds of cancers. We analyzed 9 childhood acute lymphoblastic leukemia (ALL) samples, 5 acute myelocytic leukemia (AML) samples, and 10 adult T-cell leukemia (ATL) samples having MSI to determine whether they had mutations of the E2F4, TGF-betaRII, BAX, IGFIIR, and hMSH3 genes. Frameshift mutations were 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 mutations were found in the TGF-betaRII, BAX, IGFIIR, and hMSH3 genes. E2F4 is a transcription factor that influences the cell-cycle progression. These results suggest that mutations of the E2F4 gene, presumably caused by an abnormality of one of the DNA repair genes, may play an important role in development of ATL and childhood ALL. (Blood. 2000;95:1509-1510)
authors.affiliation: Department of Internal Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Komatsu
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Ikezoe
authors.forename: T
authors.initials: T
authors.lastname: Tasaka
authors.forename: Y
authors.initials: Y
authors.lastname: Hatta
authors.forename: H
authors.initials: H
authors.lastname: Machida
authors.forename: I K
authors.initials: IK
authors.lastname: Williamson
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
authors.forename: H
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D050704:E2F4 Transcription Factor; D005091:Exons; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics; D018895:Microsatellite Repeats; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D051028:bcl-2-Associated X Protein
chemical_list: D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1