Table 9.
Whole-genome sequencing studies on hepatobiliary and pancreatic cancers.
| Cancer Type | N | Findings | Clinical Implications | Reference |
|---|---|---|---|---|
| PDA | 3 | KRAS signaling pathway was the most heavily impacted pathway | Larger WGS studies are required for assessing clinical utility | [156] |
| HCC with pulmonary metastasis | 4 | Somatic SNVs, SVs and CNAs were similar between primary and metastatic tumors | Larger studies with multiple biopsies are required to investigate similarities and differences between primary and metastatic tumors | [157] |
| FLC | 10 | Few coding, somatic mutations, no recurrent SVs Molecular differentiation from HCC |
This study supports further research on the DNAJB1-PRKACA fusion protein for potential diagnostic and therapeutic clinical implementation | [158] |
| HCC | 22 * |
TERT alterations were identified in 68% of the patients AXIN1 was more frequently mutated in HBV-positive and ARID1A in non-virus cases Druggable kinase alterations were rarely found (<2%) |
Mutations in genes coding for metabolic enzymes, chromatin remodelers and mTOR pathway could provide diagnostic and therapeutic potential | [155] |
| HBV-related HCC | 22 (WGS and RNA seq.) | Mutations, including non-coding alterations and SVs and virus integrations can create diverse transcriptomic aberrations | Integrative analysis of WGS and RNA-Seq is crucial for understanding the importance of comprehensive GA identification, shaping new diagnostic and therapeutic avenues | [159] |
| HCC | 27 (25 HBV- or HCV-related) | In the two multicentric tumors, WGS analysis suggested origins from independent mutations Chromatin regulation genes (ARID1A, ARID1B, ARID2, MLL, MLL3) were mutated in approximately 50% of the tumors Frequent integration of HBV DNA in TERT locus |
GAs and carcinogenesis can be influenced by the etiological background (viral hepatitis) Further elucidation on the molecular background of HCC is required to achieve significant clinical benefit |
[160] |
| HCC | 42 (WGS, WES and whole-transcriptome seq.) | More (TP53, CTNNB1 and AXIN1) or less (BAP1 and IDH1) frequent mutations and a novel deletion in CTNNB1 were identified; LAMA2 was a predictor of recurrence and poor survival | Identification of GAs and virus-associated genomic changes provide new predictive and therapeutic potential | [161] |
| HCC | 88 (81 HBV positive) | HBV integration is more frequent in the tumors (86.4%) than in adjacent liver tissues (30.7%) Recurrent HBV integration in TERT, MLL4 and CCNE1 genes, with upregulated gene expression |
The number of HBV integrations is associated with survival and could have prognostic significance | [162] |
| HCC/LCB | 90 (30 LCB, 60 HCC) | LCBs feature recurrent mutations in TERT promoter, chromatin regulators (BAP1, PBRM1 and ARID2), a synapse organization gene (PCLO), IDH genes and KRAS
KRAS and IDH mutations were more frequent in hepatitis-negative LCBs and are associated with poor disease-free survival |
Chronic hepatitis has a major impact on the mutational status of liver cancer | [163] |
| PDA | 100 (WGS and CNV analysis) | Identification of altered genes (TP53, SMAD4, CDKN2A, ARID1A and ROBO2), novel gene mutations (KDM6A and PREX2) and frequent targetable gene mutations (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA) | KDM6A and PREX2 are potential biomarkers and therapeutic targets | [164] |
| HCC, ICC | 300 (268 HCC, 24 ICC, 8 combined HCC/ICC) | Mutations related to liver carcinogenesis and recurrently mutated coding and noncoding regions were identified Known (CDKN2A, CCND1, APC, and TERT) and novel (ASH1L, NCOR1, and MACROD2) cancer-related genes were identified in SV analysis |
WGS is crucial for detection of cancer driver genes Association of risk factors (smoking, HCV, HBV, alcohol) with specific mutations can predict tumorigenesis and provide prognostic potential |
[10] |
Copy number alteration (CNA); fibrolamellar carcinoma (FLC); genomic alterations (GA); hepatocellular carcinoma (HCC); intrahepatic cholangiocarcinoma (ICC); liver cancer displaying biliary phenotype (LCB); pancreatic ductal adenocarcinoma (PDA); single nucleotide variation (SNV); structural variation (SV); whole-exome sequencing (WES); whole-genome sequencing (WGS); * 452 cases of WES are included in Table 5A.