Genome-wide variation analysis of formalin fixed paraffin embedded pulmonary metastatic tumor samples of osteosarcoma patients

Nil, Zelha
Osteosarcoma (OS) is a type of cancer that starts in the bone. It generally occurs in the cells called osteoblasts which form matrix of the bone. It is the most common malignant tumor of bone with an incidence rate of 19% among all cancer types. The vast majority of OS patients have pulmonary metastases at the time they are diagnosed, and about half develop lung disease later. Moreover, pulmonary metastatic tumors lead to poor prognosis and increased death rate. Although mutations in the genes coding for p53, Rb, fos and myc were detected in pulmonary metastatic tumors of OS, there is no unique genetic pathway identified for progression of pulmonary metastasis. In this research, a genome wide association study (GWAS) using FFPE samples from lung tissue of 9 patients with pulmonary metastatic OS was performed. Among 358 associated SNPs, rs6499861, rs10884554 and rs12154602 were found to be associated with metastatic OS most significantly. Moreover, second wave analysis of GWAS results provided the significant genes and pathways associated with metastatic OS. A methodology for copy number aberration and LOH analysis of SNP array data of a FFPE sample was generated using R-aroma package. Results were obtained by three different methods, namely, CalMaTe, TumorBoost and Virtual Normal algorithm. Among these, CalMaTe was found to produce less noisy data than VN Algorithm during total copy number segmentation. LOH analysis could only be performed for one sample with the second method due to poor data quality of the other samples. According to the results of copy number aberration and LOH analysis of one tumor sample T8, copy number gains in 1p31.1, 6p21.32, 7p14.3, 11q22.1, 12p12.1, and 18q12.1 chromosomal regions and copy number losses in 2p16.2, 8q24.13, 17q23.3 and 17q21.31 chromosomal regions have been found. Moreover, LOH events were observed in 2q14.3, 11q13.4, 18p11.21, 19q12, 20p13 and 23q21.1 chromosomal regions. Identification associated SNPs and significant copy number changes may be helpful in investigation of potential diagnostic and prognostic markers in metastatic osteosarcoma.
Citation Formats
Z. Nil, “Genome-wide variation analysis of formalin fixed paraffin embedded pulmonary metastatic tumor samples of osteosarcoma patients,” M.S. - Master of Science, Middle East Technical University, 2012.