Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1509-1510
BRIEF REPORT
Mutations of the E2F4 gene in hematological
malignancies having microsatellite instability
Naoki Komatsu,
Seisho Takeuchi,
Takayuki Ikezoe,
Taizo Tasaka,
Yoshihiro Hatta,
Hisanori Machida,
Ian K. Williamson,
Claus R. Bartram,
H. Phillip Koeffler, and
Hirokuni Taguchi
Department of Internal Medicine, Kochi Medical School, Nankoku,
Japan; Department of Internal Medicine, Kagawa Prefectural Central
Hospital, Takamatsu, Japan; School of Medicine, Nihon University,
Tokyo, Japan; Division of Hematology/Oncology, Cedars-Sinai Research
Institute, UCLA School of Medicine, Los Angeles, CA; and the Institute
of Human Genetics, University of Heidelberg, Heidelberg, FRG.
Mutations of coding repeats within the E2F4, TGF-
RII, 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-RII, 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-RII, 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.
