Calcifying epithelial odontogenic (Pindborg) tumor-associated amyloid consists of a novel human protein.
Calcifying epithelial odontogenic tumors (CEOTs), also known as Pindborg tumors, are characterized by the presence of squamous-cell proliferation, calcification, and, notably, amyloid deposits. On the basis of immunohistochemical analyses, the amyloidogenic component had heretofore been deemed to consist of cytokeratin-related or other molecules; however, its chemical composition had never been elucidated. We have used our microanalytic techniques to characterize the protein nature of CEOT-associated amyloid isolated from specimens obtained from 3 patients. As evidenced by the results of amino-acid sequencing and mass spectrometry, the fibrils were found to be composed of a polypeptide of approximately 46 mer. This component was identical in sequence to the N-terminal portion of a hypothetical 153-residue protein encoded by the FLJ20513 gene cloned from the human KATO III cell line. That the amyloid protein was derived from this larger molecule was demonstrated by reverse transcription-polymerase chain reaction amplification of tumor-cell RNA where a full-length FLJ20513 transcript was found. Furthermore, immunohistochemical analyses revealed that the amyloid within the CEOTs immunostained with antibodies prepared against a synthetic FLJ20513-related dodecapeptide. Our studies provide unequivocal evidence that CEOT-associated amyloid consists of a unique and previously undescribed protein that we provisionally designate APin.
Solomon
Alan
A
Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville 37920, USA. asolomon@mc.utmck.edu
Murphy
Charles L
CL
Weaver
Kristal
K
Weiss
Deborah T
DT
Hrncic
Rudi
R
Eulitz
Manfred
M
Donnell
Robert L
RL
Sletten
Knut
K
Westermark
Gunilla
G
Westermark
Per
P
D000293:Adolescent; D000595:Amino Acid Sequence; D000682:Amyloid / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000906:Antibodies; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D018333:Odontogenic Cyst, Calcifying / Q000737:chemistry* / Q000473:pathology*
D000682:Amyloid; D000906:Antibodies; D009363:Neoplasm Proteins; C480049:ODAM protein, human