Int J Med Sci 2006; 3(4):148-151. doi:10.7150/ijms.3.148
Short Research Communication
Mutation Analysis of hCDC4 in AML Cells Identifies a New Intronic Polymorphism
Department of Hematology, Oncology and Transfusion Medicine, Charité, University Hospital Benjamin Franklin, Berlin, Germany
Nowak D, Mossner M, Baldus CD, Hopfer O, Thiel E, Hofmann WK. Mutation Analysis of hCDC4 in AML Cells Identifies a New Intronic Polymorphism. Int J Med Sci 2006; 3(4):148-151. doi:10.7150/ijms.3.148. Available from http://www.medsci.org/v03p0148.htm
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.
Keywords: hCDC4, AML, Mutation Analysis, SNP