Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma

Ramli, Mohd Rozi (2019) Elucidating the Underlying Molecular Pathways Mediating Chromosomal Instability in Human Osteosarcoma. Masters thesis, Universiti Malaysia Sarawak.

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Abstract

Osteosarcoma is the most common primary malignancy of bone with worldwide incidence of 2 to 4 million/year. This tumor usually developed at distal part of fast growing bone and associated with instability of chromosome 6. Despite that, the preceding molecular mechanism leading to the instability is not fully known. Following the local ethical committee review, a total of 31 cases within 12 years were collected to investigate the copy number of gene encoding Vascular Endothelial Growth Factor (VEGF) located at chromosome 6p21 using Fluorescence in situ Hybridization (FISH) and the general chromosomal instability as indicated by micronuclei formation. In addition to VEGF, Hypoxia inducible factor 1α (HIF-1α) and p53 diagnostic immunohistochemistry (IHC) staining were performed as to investigate relationship of hypoxic stress and tumor growth suppress. Furthermore, the Mitogen Activated Protein Kinase (MAPK) cellular proliferation pathway molecules; ERK, p38 and JNK IHC were also examined. Findings showed VEGF expression at both protein and gene level (6p21). On top of that, expressed ERK, p38 but not JNK; and expressed HIF & p53 in those cases suggest tumor cell survival by evading the natural cell death program, apoptosis. In conclusion, this study presented a possible molecular mechanism underlying chromosomal instability in human osteosarcoma.

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