ArticleGenome biology2014
Diverse modes of genomic alteration in hepatocellular carcinoma.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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76 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
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- Temporal trends and patterns for early- and late-onset adult liver cancer incidence vary by race/ethnicity, subsite, and histologic type in the United States from 2000 to 2019.Cancer causes & control : CCC · 2025Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Exploration of ANKRD27 as an immune-related prognostic factor in pan-cancer and hepatocellular carcinoma.Frontiers in oncology · 2024Article
- Current status and perspectives of genetic testing in gastrointestinal cancer (Review).Oncology letters · 2024Review
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- Comprehensive analysis of immune-related lncRNAs and their clinical relevance in gastric adenocarcinoma.Functional & integrative genomics · 2023Article
- Identify and validate RUNX2 and LAMA2 as novel prognostic signatures and correlate with immune infiltrates in bladder cancer.Frontiers in oncology · 2023Article
- Lama2 And Samsn1 Mediate the Effects of Brn4 on Hippocampal Neural Stem Cell Proliferation and Differentiation.Stem cells international · 2023Article
- Uncovering novel mutational signatures byCell genomics · 2022Article
- HBV genome-enriched single cell sequencing revealed heterogeneity in HBV-driven hepatocellular carcinoma (HCC).BMC medical genomics · 2022Article
- Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers.Cancer genetics · 2022Article
- Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma.Computational and structural biotechnology journal · 2022Article
- Genomic profiling and network-level understanding uncover the potential genes and the pathways in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?International journal of molecular sciences · 2021Review
- Characterization of genomic clones by targeted deep sequencing of ctDNA to monitor liver cancer.Translational cancer research · 2021Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53, AXIN1, and CTNNB1 as the most frequently mutated genes. Lower frequency mutations have been reported in ARID1A, ARID2 and JAK1. In addition, hepatitis B virus (HBV) integrations into the human genome have been associated with HCC.
resultsHere, we deep-sequence 42 HCC patients with a combination of whole genome, exome and transcriptome sequencing to identify the mutational landscape of HCC using a reasonably large discovery cohort. We find frequent mutations in TP53, CTNNB1 and AXIN1, and rare but likely functional mutations in BAP1 and IDH1. Besides frequent hepatitis B virus integrations at TERT, we identify translocations at the boundaries of TERT. A novel deletion is identified in CTNNB1 in a region that is heavily mutated in multiple cancers. We also find multiple high-allelic frequency mutations in the extracellular matrix protein LAMA2. Lower expression levels of LAMA2 correlate with a proliferative signature, and predict poor survival and higher chance of cancer recurrence in HCC patients, suggesting an important role of the extracellular matrix and cell adhesion in tumor progression of a subgroup of HCC patients.
conclusionsThe heterogeneous disease of HCC features diverse modes of genomic alteration. In addition to common point mutations, structural variations and methylation changes, there are several virus-associated changes, including gene disruption or activation, formation of chimeric viral-human transcripts, and DNA copy number changes. Such a multitude of genomic events likely contributes to the heterogeneous nature of HCC.
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