Pharmacogenomics role and personalized medicine in osteosarcoma patients (RSPL2.3)

Abstract

Abstract The presence of malignant mesenchymal cells producing osteoid or immature bone defines Osteosarcoma (OS). It is the most common primary bone tumor in children and adolescents, accounting for approximately 5% of childhood tumors. OS has a bimodal age distribution, with peaks in adolescence and older adults. The metaphysis of long tubular bones is the most common site of OS, while it is rare in the spine, pelvis, and sacrum. In the 1970s, amputation was the standard treatment for OS, but the survival rate was less than 20%. The combined limb salvage treatment and neoadjuvant chemotherapy in the 1980s increased the survival rate to nearly 80%, but there has not been any improvement since then. Long noncoding RNAs (LncRNAs) are 200 nt length RNA molecules that can regulate gene expression. HOTAIR, a well-known LncRNA, is involved in the pathogenesis and progression of multiple tumors, but little is known about the role of gene polymorphisms in the carcinogenesis of OS. Understanding the different possible causes of pathogenesis could aid in improving OS treatment and survival. Aim: the study aims to Investigate the role of Single nucleotide polymorphism in Hox transcript anti- sense RNA (HOTAIR) in Osteosarcoma Pediatric Patients in the Egyptian population, two single nucleotide polymorphisms were selected in line with literatures supporting the association of the selected single nucleotide polymorphisms with osteosarcoma, the selected single nucleotide polymorphisms were rs920778 and rs7958904. Methods: 90 blood samples were collected retrospectively obtained from the biobank, followed by DNA extraction of blood samples using QIAamp kits prior to QPCR amplification and genotyping performed. Finally, data analysis was conducted using the R program and SPSS. Results : 90 samples were collected, however, only the clinical data of 50 patients was obtained, our findings revealed the existence of SNP rs920778 in all the patients, where 22 patients 44% harbored Heterozygous Allele 1/Allele 2 , 12 patients 24% harbored Homozygous Allele 1/Allele 1 and 16 patients 32% harbored Homozygous Allele 2/Allele 2 , while in SNP rs7958904 23 patients , 46 % don’t harbor the SNP at all while 13 patients ,26% harbored the homozygous Allele2/Allele2, and 14, 28 % harbored the heterozygous Allele1/Allele2, Patients’ clinical characteristics were associated with SNP rs920778 and SNP rs7958904 revealing interindividual variation between patients