title: Allelic loss of the ING gene family loci is a frequent event in ameloblastoma.
abstract: Ameloblastoma is the most frequently encountered odontogenic tumor, characterized by a locally invasive behavior, frequent recurrences, and, although rare, metastatic capacity. Loss or inactivation of tumor suppressor genes (TSGs) allows cells to acquire neoplastic growth. The ING family proteins are tumor suppressors that physically and functionally interact with p53 to perform important roles in apoptosis, DNA repair, cell cycle regulation, and senescence. TP53 genetic alterations were reported to infrequently occur in ameloblastoma. Considering that other TSGs related to TP53 could be altered in this tumor, we focused our study on the ING family genes. We analyzed the loss of heterozygosity (LOH) status of the ING family (ING1-ING5) chromosomal loci in a group of ameloblastomas by microsatellite analysis, and correlated the ING LOH status with clinicopathological characteristics. By using specific microsatellite markers, high frequency of LOH was found at the loci of each ING gene family member (33.3-72.2%). A significant relationship was shown between LOH of D2S 140 (ING5 locus) and solid tumor type (p = 0.02). LOH of ING3MS (ING3 locus) was also high in solid type tumors, showing a near significant association. In addition, a notable tendency toward higher LOH for half of the markers was observed in recurrent cases. LOH of ING family genes appears as a common genetic alteration in solid ameloblastoma. The current study provides interesting novel information regarding the potential prognostic significance of the allelic loss of the ING gene family loci in ameloblastoma tumorigenesis.
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Borkosky
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gunduz
authors.forename: Levent
authors.initials: L
authors.lastname: Beder
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
authors.forename: Ryo
authors.initials: R
authors.lastname: Tamamura
authors.forename: Esra
authors.initials: E
authors.lastname: Gunduz
authors.forename: Naoki
authors.initials: N
authors.lastname: Katase
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Rodriguez
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000564:Ameloblastoma / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007573:Jaw Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C501503:ING1 protein, human; C459806:ING3 protein, human; C483230:ING4 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins