Evidence of molecular alterations in the tumour suppressor gene WWOX in benign and malignant bone related lesions of the jaws

Abstract

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.

Alteration of WWOX in human cancer, a clinical view

“…They also found WWOX protein levels in four out of nine metastatic OS samples to be below those of primary tumor samples. 80 Complementary results showing the influence of reduced WWOX expression on mRNA level were reported by Diniz et al 81 in several different bone lesions: two OSs, two fibrosarcoma, and eight ossifying fibroma. Yang et al 79 reported the presence of deletions in the WWOX gene region in six out of 10 OS samples based on comparative genomic hybridization analysis, and undetectable levels of WWOX protein in 61.1% (33/54) of OSs, based on immunohistochemistry staining.…”

Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function

“…Several studies have demonstrated that WWOX inactivation is associated with a more aggressive tumor behavior in different cancers 10 26 . Our previous data and others showed that WWOX expression is absent or reduced in the majority of OS 12 13 14 27 and that restoring WWOX levels in OS cell lines results in inhibition of tumorigenicity 12 . Here we demonstrated, for the first time, that WWOX also attenuates metastatic potential of OS cells.…”

“…In particular, we showed that WWOX expression, as assessed by immunohistochemistry, is often reduced or absent in primary OS samples but also in paired samples from patients who had a pre-treatment OS biopsy and a post-treatment metastastectomy 12 suggesting that low levels of WWOX are associated with a more aggressive disease at the metastatic site. Other studies in human OS revealed frequent alterations of the WWOX gene by genome-wide array CGH analysis 13 , of WWOX mRNA by real-time PCR 14 and of WWOX protein by immunohistochemical staining 13 . When WWOX loss is modeled in mice, Wwox null mice die prematurely at age of 3–4 weeks with metabolic and neurological disorders 15 16 17 18 .…”

Trabecular Ossifying Fibroma: A Rare Case Report

“…[8] According to the WHO classification of odonogenic tumors, 2005, JOF is further subdivided into juvenile psammomatoid OF (JPOF) and juvenile trabecular OF. [2,9,10] JPOF shows calcifications corresponding to psammoma like bodies. [2] Unlike the conventional slow growing OF, JOF occurs more often in children and young adults.…”