Determination of the genomic profile that might be the treatment target in paranasal sinus carcinogenesis
Project no. 22306 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
Paranasal sinus tumors are a rare and heterogeneous type of cancer. The fact that the five-year survival rate is below fifty percent, and that the tumor focus must be removed in such a way that the patient cannot perform basic functions such as vision, hearing and nutrition, means that the quality of life for the survivors decreases significantly. The fact that treatment options in this cancer are limited to surgical intervention and conventional therapy methods cause patients to be deprived of modern "targeted treatment" approaches. Current cancer treatment approaches focus on targeted therapies. For this purpose, determining the genetic profiles of all cancers is very important in terms of revealing the treatment targets. In this context, the main aim of our study is to determine the genomic alterations that will help to illuminate the molecular biology of the disease and contribute to the clinical process of the patients, and to define drug recommendations for these targets, and to simultaneously identify cell specific cells for these cancer cells, based on the limited current genetic information. is to provide a targeted treatment strategy by identifying surface markers. For this purpose, the study material of our project consisted of DNA and RNA materials isolated from the samples, which were approved by the ethics committee numbered 20-4.2T/24 dated 29.04.2020. Mutations involved in disease pathology were determined by next-generation sequencing, and cell surface markers specific to cancer type were determined simultaneously with real-time PCR studies. As a result of next generation sequencing analysis, a total of 28,420 variants (11,353 unique variants) were identified in 30 cases. While 10% of these variants have been previously described, approximately 90% are variants identified for the first time. 1,747 unique variants with pathogenic and possibly pathogenic features in exon regions have been described for the first time in the literature. When evaluated at the gene level, the highest number of variants, pathogenic and possibly pathogenic variants were determined in the ERBB2 gene. At least one pathogenic or possibly pathogenic EGFR variation was detected in all cases. In addition, frequent variations were detected in the 5'UTR of the TP53 gene and the 3'UTR of the promoter, KRAS. When the gene expression results were evaluated, the expression level of the VCAM1 gene was determined to be significantly higher than the control. As a result, our findings are very important in terms of determining the treatment targets in paranasal sinus tumors. We predict that these findings will be very important in terms of the clinic of this rare cancer type.