Abstract
Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor; the survival is related to the response to chemotherapy and development of metastases. KMT2C is a chromatin-modifying and remodelling protein and its expression has never been studied in osteosarcoma. The aim of this study was to understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic progression to identify a new molecular target and to provide new therapeutic approach.We performed the immunohistochemical and gene expression analysis of KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic-pathological data and we analysed the expression of genes involved in the metastatic pathway in four osteosarcoma cell lines by blocking the KMT2C expression using siRNA.We found a nuclear-cytoplamic trafficking of KMT2C and the cytoplasmic localization was higher than the nuclear localization (p < 0.0001). Moreover, the percentage of cells with cytoplasmic positivity increased from low grade primary tissue to metastatic tissues. The cytoplasmic localization of KMT2C could lead to a change in its function supporting osteosarcoma carcinogenesis and progression. Our hypothesis is that KMT2C could affect the enhancer activity of genes influencing the invasive properties and metastatic potential of osteosarcoma.
Highlights
Despite osteosarcoma being considered an uncommon cancer, it represents the primitive, nonhaematopoietic, malignant tumor of the bone that is commonly found [1,2]
We evaluated the KMT2C immunohistochemical expression of 32 samples on Tissue MicroArray (TMA) sections and we observed that all osteosarcoma samples showed cytoplasmic expression of KMT2C and 31/32 (97%) osteosarcoma samples showed nuclear localization (Figures 1, 2)
One sample did not show the nuclear localization of KMT2C; this was a patient with high-grade osteosarcoma of the femur, follow-up was 6 years, he responded to neoadjuvant chemotherapy and did not develop metastasis
Summary
Despite osteosarcoma being considered an uncommon cancer, it represents the primitive, nonhaematopoietic, malignant tumor of the bone that is commonly found [1,2]. Patients’ survival is related to the development of metastasis and the response to chemotherapy [5]. The 5-year survival rate for patients with osteosarcoma without evidence of metastasis is 60–65%, whereas it is only 20–28% for osteosarcoma patients with metastases at the time of diagnosis [6,7].
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