Convergent somatic mutations in metabolism genes in chronic liver disease
Open accessAbstract
The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20-30 cancer genes 1-8. Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease 9-13 than in normal liver 13-16, which enables positive selection to shape the genomic landscape 9-13. Here we analysed somatic mutations from 1,590 genomes across 34 liver samples, including healthy controls, alcohol-related liver disease and non-alcoholic fatty liver disease. Seven of the 29 patients with liver disease had mutations in FOXO1, the major transcription factor in insulin signalling. These mutations affected a single hotspot within the gene, impairing the insulin-mediated nuclear export of FOXO1. Notably, six of the seven patients with FOXO1 S22W hotspot mutations showed convergent evolution, with variants acquired independently by up to nine distinct hepatocyte clones per patient. CIDEB, which regulates lipid droplet metabolism in hepatocytes 17-19, and GPAM, which produces storage triacylglycerol from free fatty acids 20,21, also had a significant excess of mutations. We again observed frequent convergent evolution: up to fourteen independent clones per patient with CIDEB mutations and up to seven clones per patient with GPAM mutations. Mutations in metabolism genes were distributed across multiple anatomical segments of the liver, increased clone size and were seen in both alcohol-related liver disease and non-alcoholic fatty liver disease, but rarely in hepatocellular carcinoma. Master regulators of metabolic pathways are a frequent target of convergent somatic mutation in alcohol-related and non-alcoholic fatty liver disease.
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In NASH livers, convergent mutations were identified in genes central to insulin signaling and lipogenesis.
“In NASH livers, Ng et. al. identified convergent mutations in genes central to insulin signaling and lipogenesis6.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [6]
The indexed Abstract reports independently arising mutations in FOXO1, a gene involved in insulin signalling, and GPAM, which produces storage triacylglycerol. It describes samples from patients with non-alcoholic fatty liver disease, but does not establish that these findings were specifically in NASH livers; the NASH qualifier is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredTP53 and CTNNB1 mutations do not drive extensive clonal expansion events before tumor initiation.
“The HCC driver genes TP53 (tumor protein p53) and CTNNB1 (catenin beta 1) are not the most frequently observed mutant genes in the cirrhotic liver (7–9), suggesting that these mutations do not drive extensive clonal expansion events before tumor initiation.”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [9]
No passage from our copy addresses whether TP53 or CTNNB1 mutations drive extensive clonal expansion before tumor initiation. Searches for both genes and for clonal expansion in cirrhotic liver returned no relevant passage, so the claim cannot be assessed from the available evidence. (LLM, conf=0.70)
Experimental — accuracy not yet measuredAfter decades of injury, cirrhotic livers consist of millions of nodules, most of which harbor somatic mutations.
“After decades of injury, cirrhotic livers consist of millions of nodules, most of which harbor somatic mutations (7–9).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [9]
No passage from our copy addresses whether cirrhotic livers contain millions of nodules or whether most nodules harbor somatic mutations. Searches for nodules, millions, cirrhosis, and somatic mutations found no relevant passage. (LLM, conf=0.72)
Experimental — accuracy not yet measuredThe HCC driver genes TP53 and CTNNB1 are not the most frequently observed mutant genes in the cirrhotic liver.
“The HCC driver genes TP53 (tumor protein p53) and CTNNB1 (catenin beta 1) are not the most frequently observed mutant genes in the cirrhotic liver (7–9), suggesting that these mutations do not drive extensive clonal expansion events before tumor initiation.”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [9]
No passage from our copy addresses whether TP53 and CTNNB1 are among the most frequently mutated genes in cirrhotic liver. Searches for both gene names and for mutations in cirrhosis returned only bibliographic material, with no findings or page-level evidence to assess the claim. (LLM, conf=0.70)
Experimental — accuracy not yet measuredThe inefficient CreER recombination faithfully modeled the somatic mosaicism seen in human livers before cancer development.
“While this showed that CreER was not 100% efficient, it also faithfully modeled the somatic mosaicism seen in human livers before cancer development (7–9, 33).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [9]
The supplied passage contains only the paper’s title and author information (no section or page). Searches for somatic mosaicism, CreER recombination, and hepatocyte clones found no eligible passage in our copy establishing that inefficient CreER recombination faithfully models mosaicism in human livers before cancer development. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Somatic mutations are common in nonmalignant liver tissues, but mutations in cancer drivers are observed less frequently than anticipated.
“Somatic mutations are common in nonmalignant liver tissues, but mutations in cancer drivers are observed less frequently than anticipated (7–9).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [9]
The supplied passage is bibliographic metadata (no section or page), not study text. Searches for cancer-driver mutations and somatic mutations in nonmalignant liver tissue returned no substantive passage, so our available copy does not establish either part of the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredLoss-of-function mutations in metabolic enzymes that generate hepatic lipids suggest that some somatic mutations can confer increased fitness through a reversal of the driving etiology of disease.
“These loss of function mutations in metabolic enzymes that generate hepatic lipids suggest that some somatic mutations can confer increased fitness through a reversal of the driving etiology of disease.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [6]
The available copy contains only the title and author metadata, with no substantive passage or page to assess. Searches for loss-of-function mutations, hepatic lipids, increased fitness, and reversal of disease etiology found no relevant text. The title alone cannot verify the proposed mechanism. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe same mutated genes such as Gpam and Acvr2a were selected for in both mouse and human tissues.
“This concept was strengthened by the fact that the same mutated genes such as Gpam and Acvr2a were selected for in both mouse and human tissues6.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [6]
The available passages are bibliographic metadata (labelled Abstract, no page), not findings about selection in mouse and human tissues. Searches for GPAM, ACVR2A, and cross-species selection found no passage addressing the claim, so the available copy cannot verify it. (LLM, conf=0.72)
Experimental — accuracy not yet measuredAcvr2a and Gpam are two of the most recurrently mutated genes in cirrhotic tissues from alcoholic liver disease and NASH patients.
“Interestingly, Acvr2a and Gpam are two of the most recurrently mutated genes in cirrhotic tissues from alcoholic liver disease and NASH patients6.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [6]
No passage from our copy addresses whether ACVR2A and GPAM are among the most recurrently mutated genes in cirrhotic tissue from patients with alcoholic liver disease or NASH. Searches for both gene names, cirrhosis, and related descriptions returned only bibliographic material or no matching passage. (LLM, conf=0.68)
Experimental — accuracy not yet measuredMutant clone expansion and recurrent mutations within and between individuals provide compelling evidence for increased mutant clone fitness in chronic liver disease.
“Mutant clone expansion and recurrent mutations within and between individuals provide compelling evidence for increased mutant clone fitness in chronic liver disease6.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [6]
Searches for clone fitness, convergent evolution, and somatic mutations returned bibliographic material and an Abstract passage, but no relevant full-text passage. Because the available full-text passages do not establish the attributed inference, it cannot be verified under the specified evidence rule. (LLM, conf=0.62)
Experimental — accuracy not yet measuredAcross most, if not all, tissues, after an initial expansion of the stem cell pool during early life, clonal heterogeneity tends to diminish over time.
“A consistent pattern has been observed across most, if not all, tissues: after an initial expansion of the stem cell pool during early life, clonal heterogeneity tends to diminish over time (Figure 1).17-24”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [24]
No passage from our copy matched the claim. Searches for early-life stem-cell expansion, age-related changes in clonal diversity, and declining clonal heterogeneity across tissues returned no passages, so the attributed pattern cannot be verified from this source. (LLM, conf=0.70)
Experimental — accuracy not yet measuredSelected and more fit clones may share genomic events such as nonsynonymous mutations initially thought to be restricted to cancer.
“Interestingly, these selected and more fit clones may share genomic events such as nonsynonymous mutations initially thought to be restricted to cancer.17-24”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [24]
No full-text passage retrieved from our copy addresses whether selected, fitter clones carry nonsynonymous mutations previously thought to be restricted to cancer. Searches for those terms and for cancer-associated mutations in non-malignant liver returned no relevant full-text passage; the results were limited to abstract or bibliographic material, which cannot establish this verdict. (LLM, conf=0.65)
Experimental — accuracy not yet measured
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The exposome and liver disease - how environmental factors affect liver health
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Deep whole-genome analysis of 494 hepatocellular carcinomas
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Germline Mutations in <i>CIDEB</i> and Protection against Liver Disease
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Aristolochic acid-associated cancers: a public health risk in need of global action
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The translational challenges of precision oncology
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De novo detection of somatic mutations in high-throughput single-cell profiling data sets
Muyas, F., Sauer, C. M., Valle-Inclán, J. E., Li, R., Rahbari, R., Mitchell, T. J., Hormoz, S., & Cortés‐Ciriano, I. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01863-z · Cited by 112 · see citing works
“Motivated by the importance of clonal mosaicism to somatic evolution and disease 2,49 , we next assessed whether the single-cell resolution provided by SComatic permits analysis of the patterns of clonality across cell types.”
Self-citationClonal hematopoiesis, somatic mosaicism, and age-associated disease
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“Clones with increased fitness from specific mutations can certainly drive cancer 14–16 , but expanded clones can influence other diseases both directly, as in chronic liver disease, and through indirect mechanisms, such as in blood 17–21 .”
Self-citationTherapeutic opportunities for the treatment of NASH with genetically validated targets
Lindén, D., & Romeo, S. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.05.007 · Cited by 87 · see citing works
Evolutionary histories of breast cancer and related clones
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The Somatic Mosaicism across Human Tissues Network
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“Certain variant types were not analyzed in a few samples as denoted by ‘-’.”
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Self-citationSGK2 promotes prostate cancer metastasis by inhibiting ferroptosis via upregulating GPX4
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Somatic mutation and selection at population scale
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Self-citationGenome Instability and DNA Repair in Somatic and Reproductive Aging
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Age-related somatic mutation burden in human tissues
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Genetic variation across and within individuals
Yu, Z., Coorens, T. H. H., Uddin, M. M., Ardlie, K., Lennon, N. J., & Natarajan, P. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00709-x · Cited by 50 · see citing works
“Such mitigation was recently demonstrated in chronic liver diseases, in which different clones recurrently and independently acquired somatic mutations that lead to escaping disease-related toxicity 43 .”
BackgroundSelf-citationTRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability
Chen, X., Yong, H., Chen, M., Deng, C., Wang, P., Chu, S., Li, M., Hou, P., Zheng, J., Li, Z., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02583-z · Cited by 44 · see citing works
MAFLD: an optimal framework for understanding liver cancer phenotypes
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Stem cell mutations, associated cancer risk, and consequences for regenerative medicine
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Somatic mutation as an explanation for epigenetic aging
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The contribution of genetics and epigenetics to MAFLD susceptibility
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“To determine whether there is an excess of SNVs at the TERT promoter in preneoplastic cirrhotic liver, we looked for mutations in the corresponding region of sequenced whole genomes from human donors [26].”
BackgroundMethodInfluentialSelf-citationSomatic variation in normal tissues: friend or foe of cancer early detection?
Acha‐Sagredo, A., Ganguli, P., & Ciccarelli, F. D. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.09.156 · Cited by 39 · see citing works
Human-correlated genetic models identify precision therapy for liver cancer
Müller, M., May, S., Hall, H., Kendall, T. J., McGarry, L., Blukacz, L., Nuciforo, S., Γεωργακοπούλου, Α., Jamieson, T., Phinichkusolchit, N., et al. (2025) · Nature · doi:10.1038/s41586-025-08585-z · Cited by 40 · see citing works
“We decreased the AAV induction titre in specific instances (cohorts 14, 15, 23 and 24, 1.28 × 10 8 GC per mouse) to reduce the clonal burden, facilitating progression of these more aggressive models to larger individual tumours.”
InfluentialSelf-citationClonal dynamics and somatic evolution of haematopoiesis in mouse
Kapadia, C. D., Williams, N., Dawson, K. J., Watson, C. J., Yousefzadeh, M. J., Le, D. T., Nyamondo, K., Kodavali, S., Cagan, A., Waldvogel, S. M., et al. (2025) · Nature · doi:10.1038/s41586-025-08625-8 · Cited by 41 · see citing works
Self-citationProlonged persistence of mutagenic DNA lesions in somatic cells
Chapman, M. S., Mitchell, E., Yoshida, K., Williams, N., Fabre, M. A., Ranzoni, A. M., Robinson, P. S., Kregar, L. D., Wilk, C. M., Boettcher, S., et al. (2025) · Nature · doi:10.1038/s41586-024-08423-8 · Cited by 37 · see citing works
“The updated ABC analysis motivated by referee #2 comments appears to have been important in accounting for the effects of lesion loss from the observed phylogenies, though the overall conclusions remain unchanged.”
InfluentialSelf-citationBerardi, D. E., Bock-Hughes, A., Terry, A. R., Drake, L. E., Bozek, G., & Macleod, K. F. (2022) · Science Advances · doi:10.1126/sciadv.abo2510 · Cited by 37 · see citing works
“Genomic analyses also identified the CIDEB gene, which is involved in LD metabolism, as being enriched for somatic mutations linked to fatty liver disease relative to healthy control (47), while deletion of LAMP2A in mouse liver caused hepatic steatosis due to defective lipophagy (48).”
BackgroundMASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives
Karin, M., & Kim, J. Y. (2024) · Molecular Oncology · doi:10.1002/1878-0261.13685 · Cited by 43 · see citing works
“Of note, FOXO1 , CIDEB , GPAM , and AVCR2A SNVs were recurrent in MASH liver but not in healthy controls and importantly, these mutations were not found in HCC, suggesting that SNVs in MAFLD hepatocyte likely function against tumorigenesis [78,79].”
Liu, W., Huang, S., Ji, H., Kim, S. U., Yip, T. C., Wong, G. L., Petta, S., Tsochatzis, E. A., Nakajima, A., Bugianesi, E., et al. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.02.034 · Cited by 38 · see citing works
CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth
Xu, L. M., Li, L.-Z., Wu, L., Li, P., & Chen, F. (2024) · FEBS Letters · doi:10.1002/1873-3468.14823 · Cited by 37 · see citing works
“Somatic mutations in Cideb frequently occur in patients with chronic liver disease [70].”
BackgroundACMSD inhibition corrects fibrosis, inflammation, and DNA damage in MASLD/MASH
Liu, Y. J., Kimura, M., Li, X., Sulc, J., Wang, Q., Rodríguez-López, S., Scantlebery, A. M. L., Strotjohann, K., Gallart‐Ayala, H., Vijayakumar, A., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.08.009 · Cited by 37 · see citing works
“34-36 Our transcriptomic analysis in mice and humans showed a positive correlation between the expression of DNA damage-related signatures and the liver phenotypes of MASLD/MASH.”
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“32 Convergent somatic mutations in three genes that regulate lipid processing and storage, out of 1590 genomes, were observed in association with the catabolism of lipid droplets in the liver.”
BackgroundSomatic mutations in aging and disease
Ren, P., Zhang, J., & Vijg, J. (2024) · GeroScience · doi:10.1007/s11357-024-01113-3 · Cited by 29 · see citing works
Sakuma, I., Gaspar, R. C., Luukkonen, P. K., Kahn, M., Zhang, D., Zhang, X., Murray, S., Golla, J. P., Vatner, D. F., Samuel, V. T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2312666120 · Cited by 25 · see citing works
Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism
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“A landmark resequencing study revealed the presence of somatic mutations in the FOXO1 , CIDEB and GPAM genes in liver biopsy samples from people with cirrhosis secondary to MASLD or alcohol intake 98 (Fig.”
Somatic mutations in human ageing: New insights from DNA sequencing and inherited mutations
Chatsirisupachai, K., & de Magalhães, J. P. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102268 · Cited by 26 · see citing works
The origin of hepatocellular carcinoma depends on metabolic zonation
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APOBEC Mutagenesis in Cancer Development and Susceptibility
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“…SBS2 and SBS13 are either very rare or absent in hepatocellular carcinoma, testicular cancer, thyroid adenocarcinoma [14,94], and their respective non-malignant tissue types [76,77,89], implying that APOBEC mutagenesis may not play a significant role in the development of these cancer types.”
BackgroundMarchetti, A., Pelusi, S., Marella, A., Malvestiti, F., Ricchiuti, A., Ronzoni, L., Lionetti, M., Moretti, V., Bugianesi, E., Miele, L., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000000839 · Cited by 25 · see citing works
“[12,13] Importantly, clonal mutations defining CHIP, and particularly TET2 mutations, have been shown to promote liver disease progression by inducing a proinflammatory phenotype in myeloid cells homing to the liver.”
BackgroundHepatic adaptation to chronic metabolic stress primes tumorigenesis
Tzouanas, C. N., Shay, J. E. S., Sherman, M. S., Rubin, A. J., Mead, B. E., Dao, T. T., Tao, J., Lehrich, B. M., Eng, G. M., Patterson-Fortin, J., et al. (2025) · Cell · doi:10.1016/j.cell.2025.11.031 · Cited by 24 · see citing works
A pan-tissue survey of mosaic chromosomal alterations in 948 individuals
Gao, T., Kastriti, M., Ljungström, V., Heinzel, A., Tischler, A. S., Oberbauer, R., Loh, P.-R., Adameyko, I., Park, P. J., & Kharchenko, P. (2023) · Nature Genetics · doi:10.1038/s41588-023-01537-1 · Cited by 21 · see citing works
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“For example, liver samples from human patients with fatty liver disease frequently have mutations in FOXO1, CIDEB and GPAM, three master regulators of lipid processing and storage, but similar mutations are not significantly enriched in hepatocellular carcinomas from human patients [37].”
BackgroundEffects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin
Ólafsson, S., Rodríguez, E., Lawson, A. R. J., Abascal, F., Huber, A. R., Suembuel, M., Jones, P. H., Gerdes, S., Martincorena, I., Weidinger, S., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01545-1 · Cited by 23 · see citing works
“We performed Bayesian clustering of mutations based on their VAFs in different microbiopsies and used the statistical pigeonhole principle to derive a phylogenetic relationship between the clusters 8,9 (Fig.”
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FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes
Liang, C.-Q., Zhou, D., Peng, W., Chen, W.-Y., Wu, H., Zhou, Y.-M., Gu, W., Park, K., Zhao, H., Pi, L., et al. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00227-6 · Cited by 18 · see citing works
Reconstructing phylogenetic trees from genome-wide somatic mutations in clonal samples
Coorens, T. H. H., Chapman, M. S., Williams, N., Martincorena, I., Stratton, M. R., Nangalia, J., & Campbell, P. J. (2024) · Nature Protocols · doi:10.1038/s41596-024-00962-8 · Cited by 20 · see citing works
“This approach has recently been applied to construct phylogenies of polyclonal samples of normal tissues, such as the liver 41,46 .”
Self-citationClonal Hematopoiesis: Connecting Aging and Inflammation in Atherosclerosis
Polizio, A. H., Park, E., & Walsh, K. (2023) · Current Atherosclerosis Reports · doi:10.1007/s11883-023-01083-5 · Cited by 21 · see citing works
Genetics of liver disease in adults
Konkwo, C., Chowdhury, S., & Vilarinho, S. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000408 · Cited by 19 · see citing works
Zhang, X., Chang, K., Yu, J. Q., & Loomba, R. S. (2025) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-111523-023430 · Cited by 19 · see citing works
Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer
Karin, M., & Kim, J. Y. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100096 · Cited by 18 · see citing works
Tissue mosaicism following stem cell aging: blood as an exemplar
Kapadia, C. D., & Goodell, M. A. (2024) · Nature Aging · doi:10.1038/s43587-024-00589-0 · Cited by 18 · see citing works
“External exacerbations of underlying mosaicism occur in other tissues as well, for example, in the colon of patients with inflammatory bowel disease 126 and in the liver of patients with chronic liver disease 127 , both underlaid by inflammatory tissues.”
Zanotti, S., Boot, G. F., Coto‐Llerena, M., Gallon, J., Hess, G. F., Soysal, S. D., Kollmar, O., Ng, C. K. Y., & Piscuoglio, S. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.888850 · Cited by 17 · see citing works
“Of note, mutations in metabolism genes were observed in both ALD and NAFLD but less frequently in HCC (28).”
BackgroundUnveiling the Cancer Risk Nexus of the Steatotic Liver
Kim, J., & Seki, E. (2024) · Trends in endocrinology and metabolism · doi:10.1016/j.tem.2024.02.017 · Cited by 15 · see citing works
Somatic Mutations in Normal Tissues: New Perspectives on Early Carcinogenesis
Herms, A., & Jones, P. H. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-061421-012447 · Cited by 17 · see citing works
Aberrant basal cell clonal dynamics shape early lung carcinogenesis
Gómez‐López, S., Alhendi, A. S. N., Przybilla, M. J., Bordeu, I., Whiteman, Z. E., Butler, T. M., Rouhani, M. J., Kalinke, L., Uddin, I., Otter, K. E. J., et al. (2025) · Science · doi:10.1126/science.ads9145 · Cited by 16 · see citing works
“A nonparametric Bayesian hierarchical Dirichlet process (HDP) was implemented to cluster SNVs with similar variant allele frequencies (VAFs) that were called across multiple microdissections for each patient biopsy as described previously (39).”
InfluentialSelf-citationHe, L., She, X., Guo, L., Gao, M., Wang, S., Lu, Z., Guo, H.-T., Li, R., Nie, Y., Xing, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58790-7 · Cited by 16 · see citing works
“Somatic missense, nonsense, and frameshift mutations of GPAM have been identi fi ed in biopsy specimens of liver from patients with MASLD and alcohol-related liver disease 8 .”
Pilet, J., Hirsch, T. Z., Gupta, B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42418-9 · Cited by 16 · see citing works
Relationships Between Regeneration, Wound Healing, and Cancer
Maggiore, G., & Zhu, H. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062822-123558 · Cited by 16 · see citing works
Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs
Stratton, M. R., Humphreys, L., Alexandrov, L. B., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-1687 · Cited by 16 · see citing works
Self-citationSingle-cell genotype-phenotype mapping identifies therapeutic vulnerabilities in VEXAS syndromePreprint
Ganesan, S., Murray, R. M., Sotélo, J. A. L., Eton, E. O., Takashima, K., Botella, T., Beattie, K., Indart, A. C., Chraiki, N., Croizier, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.19.594376 · Cited by 16 · see citing works
Fujiwara, N., & Nakagawa, H. (2023) · Cancer Science · doi:10.1111/cas.15925 · Cited by 15 · see citing works
Emerging and potential use of CRISPR in human liver disease
Adlat, S., Vázquez-Salgado, A. M., Lee, M., Yin, D., & Wangensteen, K. J. (2023) · Hepatology · doi:10.1097/hep.0000000000000578 · Cited by 17 · see citing works
Yang, C., Tiwari, S. K., Guo, L., An, G., Zheng, H., Huang, J., Jiang, L., Bai, Z., Zhu, Y., & Wang, N. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1110909 · Cited by 15 · see citing works
“Cell Viability ð%Þ 1⁄4 ODsample-ODblank ODcontrol-ODblank 100% (2)”
A genetic hypothesis for burnt‐out steatohepatitis
Valenti, L. V. C., Romeo, S., & Pajvani, U. B. (2021) · Liver International · doi:10.1111/liv.15103 · Cited by 14 · see citing works
The many pathways driving liver inflammation in MASH
Tilg, H., Adolph, T. E., Romeo, S., & Loomba, R. S. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.02.018 · Cited by 15 · see citing works
Pelusi, S., Bianco, C., Colombo, M., Cologni, G., Poggio, P. D., Pugliese, N., Prati, D., Pigozzi, M. G., D’Ambrosio, R., Lampertico, P., et al. (2023) · Liver International · doi:10.1111/liv.15577 · Cited by 13 · see citing works
Ezhilarasan, D., Harini, K. S., Karthick, M., & Prathap, L. (2024) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23691 · Cited by 12 · see citing works
Fukumoto, T., Umakoshi, H., Iwahashi, N., Ogasawara, T., Yokomoto‐Umakoshi, M., Kaneko, H., Fujita, M., Uchida, N., Nakao, H., Kawamura, N., et al. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105087 · Cited by 13 · see citing works
“39,40 These observations, taken together, suggest that SPNs arise from an independent distinct origin as a result of positive selection of GNAS -mutated clones in adreno-cortical tissues, rather than from a common clone that branched off from a single origin.”
Somatic mutation and selection at epidemiological scalePreprint
Lawson, A., Abascal, F., Nicola, P., Lensing, S., Roberts, A., Kalantzis, G., Baez-Ortega, A., Brzozowska, N., Moustafa, J. E.-S., Vaitkute, D., et al. (2024) · medRxiv · doi:10.1101/2024.10.30.24316422 · Cited by 10 · see citing works
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Self-citationSomatic evolution following cancer treatment in normal tissue
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“In this study, we explored somatic variants and clonal dynamics in the liver of patients with end-stage CLD caused by hemochromatosis and A1AT deficiency.”
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Steatotic liver disease induces YAP/TAZ-driven cell competition that can suppress tumor initiation
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Epigenetic memory of environmental exposures as a mediator of liver disease
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“Additionally, recent theories suggest that, as an adaptation to prolonged lipotoxicity in hepatocytes in fatty liver disease, clonal selection occurs for cells with somatic mutagenesis in genes related to insulin and lipid synthesis signaling, leading to reduced fat accumulation [32, 33].”
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Evolution of Multiple Myeloma from a Genomic Perspective
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- Authors
- Ng, S. W. K., Rouhani, F. J., Brunner, S. F., Brzozowska, N., Aitken, S. J., Yang, M., Abascal, F., Moore, L., Nikitopoulou, E., Chappell, L., Leongamornlert, D., Ivovic, A., Robinson, P., Butler, T., Sanders, M. A., Williams, N., Coorens, T. H. H., Teague, J., Raine, K., Butler, A. P., Hooks, Y., Wilson, B., Birtchnell, N., Naylor, H., Davies, S. E., Stratton, M. R., Martincorena, I., Rahbari, R., Frezza, C., Hoare, M., & Campbell, P. J.
- Affiliations
- Wellcome Sanger Institute (GB)
- University of Cambridge (GB)
- Erasmus MC (NL)
- Addenbrooke's Hospital (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Corresponding author
- Hoare, Matthew
- Campbell, Peter J.
- ORCID
- Ng, Stanley W. K.
- Rouhani, Foad J.
- Brunner, Simon F.
- Brzozowska, Natalia
- Aitken, Sarah J.
- Yang, Ming
- Abascal, Federico
- Moore, Luiza
- Nikitopoulou, Efterpi
- Chappell, Lia
- Leongamornlert, Daniel
- Ivovic, Aleksandra
- Robinson, Philip
- Butler, Timothy
- Sanders, Mathijs A.
- Williams, Nicholas
- Coorens, Tim H. H.
- Teague, Jon
- Raine, Keiran
- Naylor, Huw
- Davies, Susan E.
- Stratton, Michael R.
- Martincorena, Iñigo
- Rahbari, Raheleh
- Frezza, Christian
- Hoare, Matthew
- Campbell, Peter J.
- Venue
- Nature
- Published
- 2021-10-13
- Volume
- 598
- Issue
- 7881
- Pages
- 473-478
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3206615564
- Cited by
- 190
- References
- 54
- Citations by year
- 2026: 25 · 2025: 45 · 2024: 46 · 2023: 41 · 2022: 31 · 2021: 2
- FWCI
- 12.30
- Type
- journal article
- Language
- en
- Open access
- green
- pure.eur.nl
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- European Hematology Association (TRTH182)
- Wellcome Trust
- Cancer Research UK (26813, 29681, 19924, C14303 / A17197, 21777, 24032, 22310, 27114)
- National Institute for Health and Care Research (CL-2019-14-003, CL-2016-14-004)
- Academy of Medical Sciences (SGL019\1092)
- Medical Research Council (MC_UU_12022/6)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- somatic mutations, convergent evolution, chronic liver disease, hepatocellular carcinoma, FOXO1, CIDEB, GPAM, metabolic genes, alcoholic liver disease, non-alcoholic fatty liver disease, clonal expansion, driver mutations, insulin signaling, lipid droplet metabolism, triglyceride synthesis
- MeSH terms
- Forkhead Box Protein O1, Chronic Disease, Fatty Acids, Nonesterified, Female, Humans, Insulin Resistance, Liver, Liver Diseases, Liver Diseases, Alcoholic, Male, Mutation, Triglycerides, Cohort Studies, Active Transport, Cell Nucleus, Cell Line, Tumor, Apoptosis Regulatory Proteins, Non-alcoholic Fatty Liver Disease
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