title: Deregulated HOX genes in ameloblastomas are located in physical contiguity to keratin genes.
abstract: The expression of the HOX gene network in mid-stage human tooth development mostly concerns the epithelial tooth germ compartment and involves the C and D HOX loci. To further dissect the HOX gene implication with tooth epithelium differentiation we compared the expression of the whole HOX network in human ameloblastomas, as paradigm of epithelial odontogenic tumors, with tooth germs. We identified two ameloblastoma molecular types with respectively low and high number of active HOX C genes. The highly expressing HOX C gene ameloblastomas were characterized by a strong keratinized phenotype. Locus C HOX genes are located on chromosome 12q13-15 in physical contiguity with one of the two keratin gene clusters included in the human genome. The most posterior HOX C gene, HOX C13, is capable to interact with hair keratin genes located on the other keratin gene cluster in physical contiguity with the HOX B locus on chromosome 17q21-22. Inside the HOX C locus, a 2.2 kb ncRNA (HOTAIR) able to repress transcription, in cis, along the entire HOX C locus and, in trans, at the posterior region of the HOX D locus has recently been identified. Interestingly both loci are deregulated in ameloblastomas. Our finding support an important role of the HOX network in characterizing the epithelial tooth compartment. Furthermore, the physical contiguity between locus C HOX and keratin genes in normal tooth epithelium and their deregulation in the neoplastic counterparts suggest they may act on the same mechanism potentially involved with epithelial tumorigenesis.
authors: Institute of Pathology-Molecular Pathology Division, University of Basel, Schonbeinstrasse 40, 4031 Basel, Switzerland.
authors: Giulia
authors: G
authors: Schiavo
authors: Vincenzo
authors: V
authors: D'Antò
authors: Monica
authors: M
authors: Cantile
authors: Alfredo
authors: A
authors: Procino
authors: Stefano
authors: S
authors: Di Giovanni
authors: Rossella
authors: R
authors: Valletta
authors: Luigi
authors: L
authors: Terracciano
authors: Daniel
authors: D
authors: Baumhoer
authors: Gernot
authors: G
authors: Jundt
authors: Clemente
authors: C
authors: Cillo
mesh_terms: D000328:Adult; D000564:Ameloblastoma / Q000235:genetics*; D005260:Female; D005801:Genes, Homeobox; D006801:Humans; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000235:genetics*; D007633:Keratins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007633:Keratins