ABSTRACT
WWOX is a tumour suppressor gene altered in various human neoplasms. Deletion of WWOX is associated with bone metabolic defects and development of osteosarcoma in mice. We hypothesized that alterations of this gene are associated with the development of benign and malignant mesenchymal bone related lesions of the jaws. We investigated WWOX mRNA by nested reverse transcription-PCR and direct sequencing and quantitative real-time PCR in two osteosarcoma, two fibrosarcoma, eight ossifying fibroma and two fibrous dysplasia fresh samples. Malignancy was associated with a decreased WWOX mRNA expression. Aberrant transcription pattern was found in five samples; however, the relative quantification (RQ) of the WWOX mRNA in such lesions was not different from those carrying only the wild-type. We provide new evidence of WWOX alterations in osteosarcomas and demonstrate for the first time alterations of this gene in fibrosarcomas as well as in ossifying fibromas of the jaws.
Subject(s)
Bone Neoplasms/genetics , Fibroma, Ossifying/genetics , Fibrosarcoma/genetics , Jaw Neoplasms/genetics , Oxidoreductases/genetics , Tumor Suppressor Proteins/genetics , Adolescent , Adult , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Child , Female , Fibroma, Ossifying/metabolism , Fibroma, Ossifying/pathology , Fibrosarcoma/metabolism , Fibrosarcoma/pathology , Gene Expression Regulation, Neoplastic/genetics , Genes, Tumor Suppressor , Humans , Jaw Neoplasms/metabolism , Jaw Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Oxidoreductases/metabolism , RNA, Messenger/analysis , RNA, Messenger/metabolism , Tumor Suppressor Proteins/metabolism , WW Domain-Containing Oxidoreductase , Young AdultABSTRACT
Odontogenic keratocyst (OKC) is an aggressive benign odontogenic neoplasm associated with PTCH1 alteration. PTCH1 has several isoforms generated by use of different first exon (1b, 1d and 1e). These isoforms code for proteins with different functions, expression profiles and transcriptional regulation. The aim of the present study was to investigate the expression of PTCH1 first exons in OKC tumors to shed light on scenery whereby PTCH1 coordinates OKC tumorigenesis. Forty OKC, including 12 sporadic and 28 associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS), were included in the study. The variants 1b, 1d and 1e were investigated by RT-PCR. The exon 1b was detected in 90% of OKC and none of the dental follicle (control). Most of the OKC, sporadic and syndromic, and all of the samples of dental follicles demonstrated the expression of 1d mRNA. All primary OKC had 1b mRNA while 4 (24%) lesions marsupialized lost 1b expression. In addition, the pattern of exon 1 expression observed in oral mucosa adjacent to the OKC was similar to the OKC tumor. In conclusion, this report showed overactivity of Hedgehog (HH) pathway in OKC lesion and at adjacent oral mucosa. We also demonstrated that marsupialization could alter PTCH1 variants profiling in some OKC cases.
