We performed whole exome sequencing (WES) and microarray analysis to detect somatic variants and copy number alterations (CNAs) for underlying mechanisms in a case series of hepatocellular carcinoma (HCC) with paired DNA samples from tumor and adjacent nontumor tissues. Clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status and their associations with tumor mutation burden (TMB) and CNA burden (CNAB) were evaluated. WES from 36 cases detected 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 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.

我们使用来自肿瘤和邻近非肿瘤组织的配对 DNA 样本进行了全外显子组测序 (WES) 和微阵列分析，以检测肝细胞癌 (HCC) 病例系列的潜在机制的体细胞变异和拷贝数改变 (CNA)。根据 Edmondson-Steiner (ES) 分级、巴塞罗那临床肝癌 (BCLC) 分期、复发和生存状态及其与肿瘤突变负荷 (TMB) 和 CNA 负荷 (CNAB) 的关系评估临床病理结果。36 例 WES 检测到TP53、AXIN1、CTNNB1和SMARCA4基因变异， AKT3、MYC和TERT基因扩增，以及CDH1、TP53、IRF2、RB1、RPL5和PTEN基因缺失。在大约 80% 的病例中观察到这些影响 p53/细胞周期控制、PI3K/Ras 和 β-catenin 通路的遗传缺陷。52% 的病例中检测到ALDH2基因种系变异。ES III 级、BCLC C 期和复发的预后不良患者的 CNAB 明显高于 III 级、A 期、III 级和未复发的预后良好的患者。对大型病例系列进行进一步分析，将基因组图谱与临床病理学分类相关联，可以为相关基因和通路的诊断解释、预后预测和目标干预提供证据。