71. Integrated genomic analysis of hepatocellular carcinoma using WES and aCGH

A retrospective study was conducted on a case series of hepatocellular carcinoma (HCC) using whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) to evaluate genetic defects for underlying mechanisms and clinicopathologic associations. Paired DNA samples from tumor and adjacent nontumor tissues of 36 HCC cases and their clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status were collected. Somatic variants and copy number alterations (CNAs) in a panel of key genes related to HCC were identified, and the tumor mutation burden (TMB) and CNA burden (CNAB) were calculated. An integrated genomic analysis was performed to evaluate the underlying pathways and clinicopathologic associations for HCC. The WES of the cases revealed variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and β-catenin pathways were observed in approximately 80% of the cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways. A retrospective study was conducted on a case series of hepatocellular carcinoma (HCC) using whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) to evaluate genetic defects for underlying mechanisms and clinicopathologic associations. Paired DNA samples from tumor and adjacent nontumor tissues of 36 HCC cases and their clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status were collected. Somatic variants and copy number alterations (CNAs) in a panel of key genes related to HCC were identified, and the tumor mutation burden (TMB) and CNA burden (CNAB) were calculated. An integrated genomic analysis was performed to evaluate the underlying pathways and clinicopathologic associations for HCC. The WES of the cases revealed variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and β-catenin pathways were observed in approximately 80% of the cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.