Feasibility of next generation sequencing (NGS) from Uzbekistan: A preliminary data analysis.

Abstract

e14579 Background: Molecular testing has become an important part of management of cancer patents. Due to local nonavailability and financial constrains NGS is picking up slowly in Uzbekistan. An attempt was being made to see feasibility and analyze next generation sequencing data from local population. Here we report data from first such big analysis. Methods: 76 advanced cancer patients were enrolled and tissue samples were sent for NGS. The analysis were sent to the lab for performing FOUNDATIONONER CDx (F1CDx) - the NGS based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations(indels), and copy numbers alterations(CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability(MSI), tumor mutational burden(TMB), and for selected forms of ovarian cancer, loss of heterozygosity(LOH) score, using DNA isolated from formalin-fixed, paraffin-embedded(FFPE) tumor tissue specimens. Results: Out of 76 patients (35 male 41female) there were 15/76 lung cancer patients, 13/76- breast cancer, 12/76 - colorectal, 5/76 - ovarian and other malignancies. In cohort of lung cancer, the multiple gene abnormalities detected were - EGFR-5/15; ALK-3/15; ROS-0; KRAS-1/15; NRAS-0; BRAF-1/15; MET-1/15; NTRK-3/15. In breast cancer population - BRCA1 mutation was found in - 3/13; BRCA2 in 1/13; ERBB-3/13; and ESR-1/13. In group with colorectal cancer the gene abnormalities located were - BRAF-1/12; KRAS-7/12: G12D-1; G12V-1; G12C-1; NRAS-0; MSI-3/7; MMR: MLH-1; MSH2-2; MSH3-2; MSH6-2. In ovarian cancer findings included - BRCA1 in 0/5; BRCA2-1/5; PALB-1/5; CHEK-1/5; PARP1-1/5. The most frequent genetic alteration observed in the whole group was TP53 (50/76). Commonest hereditary gene alterations besides TP53 were seen in ATM gene -12/76. A large number of Variant of Unknown Significance were also recorded. Conclusions: It is feasible to perform NGS analysis using reference laboratories. There is population of patients, willing to undergo specialized tests. Actionable molecular data information can be collected and utilized for patient care. No unique markers could be found due to small sample size.