ATBF1 geninin bir multi-tümör baskılayıcı gen olarak incelenmesi

ABSTRACTINVESTIGATION OF ATBF1 AS A MULTI-TUMOR SUPPRESSORGENEÖzkan AydemirM.S. in Molecular Biology and GeneticsSupervisor: Dr. M. Cengiz YakıcıerAugust 2005, 34 pagesATBF1 is a transcription factor which inhibits Myb oncoprotein and increasesp21 promoter activity. Recently, ATBF1 gene was shown to be expressionallydownregulated and harbored frequent mutations in prostate cancers. ATBF1resides on chromosome 16q22.3-23.1 which is deleted recurrently in numeroustypes of tumors including hepatocellular carcinoma, breast cancers, glial tumorsand colorectal cancers. In this study we aimed to assess ATBF1 gene?sinvolvement in HCC, breast cancer, glial cancers and colorectal cancersdevelopment. We analyzed the DNA samples of these tumors for ATBF1 genemutations. We focused on the regions which harbored high frequency ofmutations in prostate cancers. Our study revealed frequent 3 and 6 bppolymorphisms on glutamine rich, and therefore possible transactivationdomains. We showed homozygous 3 and 6 bp alterations were heterozygous inthe matching histologically normal tissues in 3 cases; supporting the tumorsuppressor role of ATBF1 gene in tumors tested, according to Knudson?s two-hit hypothesis. In addition, we were able to identify single base pairsubstitutions on ATBF1 gene, and one of them is highly likely to be somatic.Based on our results, we hypothesize that ATBF1 gene is a multi-tumorsuppressor gene, although further investigation of this gene is necessary.Keywords: hepatocellular carcinoma, tumor suppressor gene, chromosome16q,LOH.