| Objectives This research is to explore the relationships between tumor suppressor gene HRPT2 and ossifying fibroma of the jaws and to analyze its effects on tumorigenesis of ossifying fibroma of the jaws.Methods The lesions and corresponding peripheral bloods(with informed consent) of the ossifying fibroma of the jaws were collected in Peking University School and Hospital of Stomatology. 1 The clinical manifestations of these cases were sorted and analyzed to promote the understanding of the tumors. 2 Total DNA was extracted from the fresh lesions and the corresponding peripheral bloods. The 17 exons and slicing of HRPT2 gene were designed in 15 different fragments and amplified by PCR, and the PCR productions were analyzed via direct sequencing. 3 The expression of the parafibrmin encoded by HRPT2 gene were detected by immunohistochemical methods.Res?lts 1 We collected a total of 40 cases with sporadic ossifying fibroma and one case with multiple ossifying fibroma associated with hyperparathyroidism-jaw tumor(HPT-JT) syndrome. 2 Clinical features results: Visting ages at first presentation ranged from 1 to 47 years(media age: 19.5years). The male: female ratio is 19:21. Seventeen(44.7%, 17/38) tumors occurred in the maxilla, twenty-one(55.3%, 21/38) in the mandible. There were two multiple cases that simultaneously occurred in the maxilla and mandible. Bone or facial swelling(90%, 36/40) was the most common symptoms, and other presentations included pain(10%, 4/40), bite pain(2.5%, 1/40), nasal obstruction(5%, 2/40), numbness(7.5%, 3/40), discomfort(5%, 2/40), looseness of teeth(2.5%, 1/40), tinnitus(2.5%, 1/40) and surface fester(2.5%, 1/40). In 38 of 40 patients with available radiographs, radiographic features included radiolucent 21%(8 cases), mixed 66%(25 cases), and radioopaque lesions13%(5 cases). Lesions of 29 cases were well defined, and 9 cases were unclear. 3 HRPT2 gene mutations: Two novel HRPT2 somatic mutations were identified in 2(case#1 and case#2) sporadic OF cases and the two mutations were both located in exon 1. Case #1 deleted four bases CTTA at position 13-16(c.13-16 del CTTA); Case #2 missed three bases ACG at position 8-10 and at the same place inserted two bases CT(c.8-10 del ACGins CT). The two frameshift mutations had led to premature stop of the encoded protein. Case #1 leads to a premature stop at position 15 th codon with the fifth amino acid residue leucine as the first affected amino acid, changing into an alanine(p. Leu5Alafs*15).The frame shift of case #2 from the third amino acid residue and the aspartic acid was change into alanine(p. Asp3Alafs*18), causing a premature stop at the following 18 th codon in the new reading frame. After HRPT2 genetic testing on the HPT-JT syndrome case and his father's blood sample, we found a novel HRPT2 germline mutation(c.18 ins GTTAG) and a SNP,-10T> G(rs188082584). The mutation deleted five bases GTTAG at position 18 and led to a premature stop at position 17 th codon with the sixth amino acid residue serine as the first affected amino acid, changing into a arginine(p. Ser6 Argfs * 17). 4 Immunohistochemistry results: All the OFs showed expression of parafibromin in the nulear and sometimes in cytoplasm of the spindle shaped lesion cells including the mutation carriers.Conclusions 1 Five percents(2/40) of sporadic cases in our current research harbors HRPT2 gene mutations. It suggests that HRPT2 mutation occurs only in a few sporadic OF cases, rather than is the advantageous causative gene of sporadic OF. 2 Although HRPT2 mutation was found in only one HPT-JT case, it confirmed again that HRPT2 is the advantageous causative gene of HPT-JT... |
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