Odontogenic ameloblast-associated protein nature of the amyloid found in calcifying epithelial odontogenic tumors and unerupted tooth follicles

Abstract

We have previously reported that the amyloid found in three patients with calcifying epithelial odontogenic tumors (CEOT) was composed of N-terminal fragments of a putative 153-residue protein specified by a gene designated FLJ20513 now known to represent exons 5 through 10 of the odontogenic ameloblast-associated protein (ODAM) locus that encodes a 279-residue polypeptide. Confirmation of the amyloidogenic potential of ODAM has resulted from analyses of four other cases where we found, in addition, a 74-residue segment specified by exon 4. Through preparation of ODAM-related synthetic peptides, it was possible to localize the fibril-forming region of this molecule, as well as generate a monoclonal antibody that reacted specifically with the amyloid associated with CEOT. Notably, we also detected green birefringent congophilic material in unerupted tooth follicles - a precursor of CEOT - and demonstrated through immunologic and chemical analyses the ODAM nature of the deposits. Our studies have provided further evidence for this unique form of odontogenic amyloid that we provisionally designate "AODAM".

Expression of Odontogenic Ameloblast-Associated Protein (ODAM) in Dental and Other Epithelial Neoplasms

“…Through chemical analyses of amyloid fibrils isolated from three specimens, we found that these components were composed of N-terminal fragments of a 153-residue hypothetical protein specified by the FLJ20513 gene (a short form of ODAM cDNA cloned from the Kato III human signet-ring gastric carcinoma cell line [9,10]), where the last six of ten protein-encoding exons of ODAM are located. Subsequently, in studies of amyloid from four other CEOT cases, we identified varying amounts of a second ODAM-related protein with residues originating from the fourth exon (11). This discovery provided conclusive evidence for the transcription of a longer ODAM product that was predicted to consist of 279 amino acids, 126 of which are products of the first four coding exons (1,4).…”

Targeting the Sonic Hedgehog Pathway in Keratocystic Odontogenic Tumor

“…Studies reveled that ODAM is strongly expressed in the maturation stage of rat incisor ameloblasts and in the junctional epithelium attached to the enamel of erupted molars, as well as in the late stage of ameloblast lineage cell cultures (27,28). ODAM has been associated with other types of odontogenic tumors, namely calcifying epithelial odontogenic tumors (17,29,30). KCOT-1 cells expressed these tumor-related proteins, further confirming the neoplastic nature of these cells.…”

Oral Masses in Two Cats

“…16 Recent studies have shown that the amyloid associated with CEOTs is composed of N-terminal fragments of the ODAM. 8,12 Therefore, this unique odontogenic amyloid, formerly designated APin, is now termed ODAM. 8 Apart from CEOTs, ODAM is highly expressed by mature ameloblasts and is present in the enamel organ as well as in ameloblastomas.…”