title: Mutation analysis of hCDC4 in AML cells identifies a new intronic polymorphism.
abstract: hCDC4 (FBW7, FBXW7) is a new potential tumor suppressor gene which provides substrate specificity for SCF (Skp-Cullin-F-box) ubiquitin ligases and thereby regulates the degradation of potent oncogenes such as cyclin E, Myc, c-Jun and Notch. Mutations in the hCDC4 gene have been found in several solid tumors such as pancreas, colorectal or endometrial cancer. We carried out a mutation analysis of the hCDC4 gene in 35 samples of patients with Acute Myeloid Leukemia (AML) to elucidate a possible role of hCDC4 mutations in this disease. By direct DNA sequencing and digestion with Surveyor nuclease one heterozygous mutation in the 5' untranslated region of exon 1, transcript variant 3 was detected. Additionally, we could identify a new intronic SNP downstream of exon 10. The new variation was present in 20% of AML samples and was furthermore confirmed in a panel of 51 healthy individuals where it displayed a frequency of 14%. In conclusion we provide first data that in contrast to several solid tumors, mutations in the hCDC4 gene may not play a pivotal role in the pathogenesis of AML. Furthermore, we describe a new intronic polymorphism with high frequency in the intron sequence of the hCDC4 gene.
authors.affiliation: Department of Hematology, Oncology and Transfusion Medicine, Charité, University Hospital Benjamin Franklin, Berlin, Germany. daniel.nowak@charite.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Nowak
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mossner
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.forename: Olaf
authors.initials: O
authors.lastname: Hopfer
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann