ArticleOncotarget2016
Inferring the progression of multifocal liver cancer from spatial and temporal genomic heterogeneity.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.International journal of molecular sciences · 2023Pooled it
- Hepatocellular carcinoma metastasis-immune microenvironment crosstalk: emerging mechanisms and immunotherapy.Cellular & molecular biology letters · 2026Review
- Characteristics of Recurrent Hepatocellular Carcinoma Based on Serum AFP, PIVKA-II, and Genetic Mutations.Medicina (Kaunas, Lithuania) · 2026Article
- Multi-omics profiling reveals that ScissorCellular oncology (Dordrecht, Netherlands) · 2026Article
- Intrahepatic Microbial Heterogeneity in Multifocal Hepatocellular Carcinoma and Its Association with Host Genomic and Transcriptomic Alterations.Cancer discovery · 2025Article
- Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma.British journal of cancer · 2023Article
- Hepatitis B Virus-Associated Hepatocellular Carcinoma.Viruses · 2022Review
- Clinical Evidence and Selecting Patients for Treatment with Erdafitinib in Advanced Urothelial Carcinoma.OncoTargets and therapy · 2022Review
- A pan-cancer analysis of FAT atypical cadherin 4 (FAT4) in human tumors.Frontiers in public health · 2022Article
- Transcriptomic analysis links hepatocellular carcinoma (HCC) in HZE ion irradiated mice to a human HCC subtype with favorable outcomes.Scientific reports · 2021Article
- Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.PLoS genetics · 2021Article
- Deciphering Tumor Heterogeneity in Hepatocellular Carcinoma (HCC)-Multi-Omic and Singulomic Approaches.Seminars in liver disease · 2021Review
- Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies.World journal of gastroenterology · 2020Review
- Tumour evolution in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2020Review
- Limited bias effect of intratumoral heterogeneity on genetic profiling of hepatocellular carcinoma.Journal of gastrointestinal oncology · 2020Article
- Article
- Targeted genomic profiling identifies frequent deleterious mutations in FAT4 and TP53 genes in HBV-associated hepatocellular carcinoma.BMC cancer · 2019Article
- Fibroblast growth factor receptors as treatment targets in clinical oncology.Nature reviews. Clinical oncology · 2019Review
- Identifying Clonal Origin of Multifocal Hepatocellular Carcinoma and Its Clinical Implications.Clinical and translational gastroenterology · 2019Review
- Detecting virus integration sites based on multiple related sequencing data by VirTect.BMC medical genomics · 2019Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multifocal tumors developed either as independent tumors or as intrahepatic metastases, are very common in primary liver cancer. However, their molecular pathogenesis remains elusive. Herein, a patient with synchronous two hepatocellular carcinoma (HCC, designated as HCC-A and HCC-B) and one intrahepatic cholangiocarcinoma (ICC), as well as two postoperative recurrent tumors, was enrolled. Multiregional whole-exome sequencing was applied to these tumors to delineate the clonality and heterogeneity. The three primary tumors showed almost no overlaps in mutations and copy number variations. Within each tumor, multiregional sequencing data showed varied intratumoral heterogeneity (21.6% in HCC-A, 20.4% in HCC-B, 53.2% in ICC). The mutational profile of two recurrent tumors showed obvious similarity with HCC-A (86.7% and 86.6% respectively), rather than others, indicating that they originated from HCC-A. The evolutionary history of the two recurrent tumors indicated that intrahepatic micro-metastasis could be an early event during HCC progression. Notably, FAT4 was the only gene mutated in two primary HCCs and the recurrences. Mutation prevalence screen and functional experiments showed that FAT4, harboring somatic coding mutations in 26.7% of HCC, could potently inhibit growth and invasion of HCC cells. In HCC patients, both FAT4 expression and FAT4 mutational status significantly correlated with patient prognosis. Together, our findings suggest that spatial and temporal dissection of genomic alterations during the progression of multifocal liver cancer may help to elucidate the basis for its dismal prognosis. FAT4 acts as a putative tumor suppressor that is frequently inactivated in human HCC.
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