Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing. Methods: Whole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}. Results: Mutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes—identified across 10 genome sequencing studies—in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC. Conclusion: Our results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients

CTNNB1 polymorphism (rs121913407) in circulating tumor DNA (ctDNA) in Egyptian hepatocellular carcinoma patients

Abstract Background Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the fourth in Egypt. Persistent inflammation and specific somatic mutations in driving genes play a major role in the development of HCC. One of these somatic mutations is CTNNB1 mutations with subsequent activation of β-catenin in HCC, associated with a risk of malignant transformation. In this study, we investigate the clinical utility of peripheral blood circulating tumor DNA (ctDNA) CTNNB1 (rs121913407) in HCC patients compared to pathological chronic hepatitis C virus (HCV) patients and healthy controls. Methods Our study is a case-control study at the Ain Shams Centre for Organ Transplantation, Ain Shams University Hospitals, enrolling twenty-eight adult HCC patients (twelve early HCC patients and sixteen advanced HCC patients), ten patients with chronic hepatitis C as a disease control group, and ten healthy controls. We collected plasma and stored at −80 °C. We detected mutations in the gene locus CTNNB1 rs121913407 by real-time PCR. Results All of our studied cases (early and advanced HCC) in addition to HCV and healthy control groups were CTNNB1 wild (TT) genotype. There was statistical significant difference between early and late cases of HCC as regards AFP and AST. Conclusions None of our recruited subjects showed CTNNB1 rs121913407 gene mutation. Further studies on larger number of patients are needed to clarify and confirm the clinical utility of CTNNB1 single-nucleotide polymorphism in the pathogenesis of HCC related to HCV in Egyptian population