OBJECTIVETo investigate the neoplastic nature of fibrous dysplasia by molecular clonality approaches.

METHODSTwenty-one cases of fibrous dysplasia were examined by clonality assays based on X-chromosomal inactivation mosiacism. Lesional and non-lesional tissues were microdissected from paraffin sections followed by DNA extraction. The DNA was predigested by HpaII or HhaI, and then amplified by nested PCR targeting phosphoglycerate kinase (PGK) and androgen receptor (AR) genes. Single nucleotide polymorphism (SNP) at the PGK locus was identified by incubation of the PCR products with Bst XI and agarose gel electrophoresis, and CAG repeat length polymorphism at AR locus was determined by denaturing polyacrylamide gel electrophoresis and visualized by silver staining.

RESULTSMicroscopically, all 21 cases showed characteristic features of fibrous dysplasia, including spindle fibrous cell proliferation and immature bone trabeculae at various proportions. DNA polymorphisms at AR locus and SNP of PGK gene were found in 15 of 21, and 4 of 21 cases, respectively. All 19 cases were monoclonal in nature. Two cases showed no polymorphism at either AR or PGK gene locus.

CONCLUSIONSFibrous dysplasia is likely a clonal, neoplastic process. Additional studies of larger number of cases are needed for a definitive conclusion.

Adolescent ; Adult ; Child ; Child, Preschool ; Chromosomes, Human, X ; Female ; Fibrous Dysplasia of Bone ; genetics ; pathology ; Humans ; Middle Aged ; Phosphoglycerate Kinase ; genetics ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; Young Adult

Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30-50 cells (5 000-10 000 µm
DNA Copy Number Variations ; Diagnosis, Differential ; Fibroma, Ossifying/genetics* ; Fibrous Dysplasia of Bone/genetics* ; Galactosyltransferases ; Humans ; Jaw ; Neoplasm Recurrence, Local ; Nuclear Proteins

OBJECTIVETo study the significance of c-myc, p53 and p16 protein expression in fibrous dysplasia, to detect the GNAS1 gene mutation in fibrous dysplasia, and to explore the property of fibrous dysplasia.

METHODSThe expression of c-myc, p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy, 1 Mazabraud syndrome and 20 control cases (10 cases of bony callus, 10 cases of osteosarcoma). Genomic DNA extraction, PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia.

RESULTSC-myc protein immunoreactivity was detected in 91 percentage of FD (P = 0.001). Compared with the negative control group, the difference was significant. P16 positive was detected in 34 FD cases (P = 0.001). The difference was significant as compared with the positive control group. Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation. PCR amplification was successful in 12 of 35 FD cases. Two of the 12 FD cases were detected to have GNAS1 gene mutation, in which 1 case was FD of Mazabraud syndrome, 1 case was a monostotic lesion.

CONCLUSIONSC-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease. P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD. The abnormal expression of the gene p16 might play an important role in the formation of FD. The GNAS1 mutation exist in FD. All of the results indicate that FD could be a neoplasia disease, caused by multiple factors leading to a dysfunction of bone development.

Adolescent ; Adult ; Child ; Chromogranins ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Fibrous Dysplasia of Bone ; genetics ; metabolism ; pathology ; GTP-Binding Protein alpha Subunits, Gs ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Osteosarcoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Young Adult