*4.1.2 Genetic markers*

Assessment of *CCN3* expression levels at diagnosis may represent a useful molecular tool for early identification of patients with osteosarcoma. Gene alteration of c-kit protein also serves as a prognostic marker for osteosarcoma. The transcriptional regulator, Oct-4, has been found to play a marked role in proliferation and spread of cancer. A reduced expression and inactivation of miR-34 gene have been reported to be associated with osteosarcomas. The action of miR-34 is p53 dependent. A dominant polymorphic variant of TGFβ receptor 1 (TGFBR1), TGFBR1\*6A, is found to be associated with increased susceptibility of osteosarcoma for metastasis. Bcl-xL, a member of Bcl-2 (B-cell lymphoma (BCL)) protein family, has been investigated to function as a dominant regulator of apoptotic cell death and plays an important role in malignant transformation. Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule that decreases immune response mediated by T cells, promotes development of osteosarcoma. Overexpressions of *Cortactin* (*CTTN*) gene, present in 11q13 amplicon, serve as a valid biomarker for osteosarcoma [10].
