Somatic hereditary gene panel analysis: A pilot study from Uzbekistan.

Abstract

e15044 Background: Molecular diagnostics is gaining importance in routine clinical practice. Availability of actionable genetic changes in hereditary panel of genes has acquired even larger interest. This study is an attempt evaluate the limited somatic genetic alterations in small population of Uzbek patients. Methods: Somatic tumor sample material was analyzed using 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. Our focus of hereditary panel included following genes-TP53, CDH1, PTEN, STK11, PALB2, CHEK2, ATM, NBN, BARD1, BRCA1 and BRCA2. Results: Out of 76 patients analyzed 50 were found have at list one abnormal gene from the above hereditary panel. TP53 was frequent pathogenic mutation in 50 of 76 patients. Commonest hereditary gene alterations were seen in ATM gene -12/50(6%). BRCA2 mutations existed in 7 of 50(3,5%), PTEN – 6/50(3%), PALB-2 – 4/50(2%), CHEK-2 – 5/50(2,5%), NBN – 5/50(2,5%), STK11 – 3/50(1,5%), CDH1 – 2/50(1%), BRCA1-2(1%), BARD1 – 1/50(0,5%). Some patients had multiple gene combinations. One of the patients had four gene abnormality-PTEN, PALB2, CHEK2, and BRCA2.Three patients have 3(1,5%) somatic hereditary mutations, 23(11,5%) patients have two abnormal hereditary genes and 38(19%) patients had changes in single gene only. Important actionable mutations (BRCA, PALB2 and CHEK2 were found in 15(11,4%) patients. Conclusions: This is the first exploratory analysis of somatic hereditary multi-gene panel. About 11% of the patients were found to have actionable gene mutations.