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.


Development of a bone tumor model under in vitro conditions
Kömez, Aylin; Hasırcı, Vasıf Nejat; Hasırcı, Nesrin; Department of Biotechnology (2019)
Osteosarcoma is one of the most common types of primary bone cancerous tumor. The structure of this tumor is solid, hard and irregular. Three dimensional (3D) models mimicking tumor tissue are needed for screening efficacy of the anticancer drugs for an effective personalized therapy. This study describes the design and production of a 3D bone tumor model (BTM) by using tissue engineering approach, and shows its capability to assess the efficacy of an anticancer drug. The model consists of two parts: (1) po...
Structural mapping and network analysis of patient-specific mutations in glioblastoma
Kaya, Tuğba; Tunçbağ, Nurcan; Doğan, Tunca; Department of Bioinformatics (2018)
Cancer is one of the most common cause of death worldwide. It occurs as a result of a collection of somatic deviations from normal state. Therefore, many efforts have been invested to profile mutations in different types of tumors; such as, the Cancer Genome Atlas (TCGA) which deposits multiple omic data for more than 11,000 tumor samples. In this thesis, we present a pipeline which retrieves patient-specific mutation data in Glioblastoma from TCGA, maps these mutations on the protein structures in Protein ...
Analyses and modeling of ovarian cancer microarray data
Karakelle, Barış S; Purutçuoğlu Gazi, Vilda; Department of Biomedical Engineering (2019)
Ovarian cancer is one of the common cancer types among other oncological diseases. The major causes of this cancer can be listed as age, obesity, hormone therapy, material inheritance and contraceptive pills. Due to its generality and importance, many researches have been conducted from distinct labs about this illness and its plausible causes have been intensively investigated either inmicroarray studies, where just part of the related genes are detected, or in thepairwise correlation analyses between the ...
Cancer modeling via biologically validated genes
Karakelle, Barış Su; Purutçuoğlu Gazi, Vilda; Ürün, Yüksel (2017-05-10)
The cancer disease is the second most common disease type seen after the frequency of the cardiovascular diseases. The frequency of this genetic disease changes with respect to the gender. Accordingly, the gynecological cancer, which covers ovarian, endometrial or cervical cancer, is the second most common cancer type in women after the breast cancer. Similar to other cancer types, the gynecological cancer is the system disease, meaning that the malfunctions and mutations in the gene regulatory ...
Capture and release of viable CTCs in microfluidic channel
Ateş, Hatice Ceren; Şen Doğan, Begüm; Özgür, Ebru; Külah, Haluk (null; 2017-10-04)
The number of circulating tumor cells (CTCs) in blood is associated with prognosis in several types of cancer. Isolation and characterization of CTCs have important clinical significance in terms of prognosis and early detection of response to treatment. Moreover, downstream characterization of CTCs may help better patient stratification and therapy guidance. However, CTCs are extremely rare and highly sensitive and specific technology is required to isolate viable CTCs from blood cells. In this study, a su...
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.