Dysplastic nodules are premalignant neoplastic nodules found in explanted livers with cirrhosis. Genetic signatures of premalignant dysplastic nodules (DNs) with concurrent hepatocellular carcinoma (HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis. We analyzed four patients with multifocal nodular lesions and cirrhotic background by whole-exome sequencing (WES). The genomic profiles of somatic single nucleotide variations (SNV) and copy number variations (CNV) in DNs were compared to those of HCCs. The number and variant allele frequency of somatic SNVs of DNs and HCCs in each patient was identical along the progression of pathological grade. The somatic SNVs in DNs showed little conservation in HCC. Additionally, CNVs showed no conservation. Phylogenetic analysis based on SNVs and copy number profiles indicated a nonlinear segregation pattern, implying independent development of DNs and HCC in each patient. Thus, somatic mutations in DNs may be developed separately from other malignant nodules in the same liver, suggesting a nonlinear model for hepatocarcinogenesis from DNs to HCC.
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http://dx.doi.org/10.18632/oncotarget.10502 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
The present research was performed to examine the possible capability of allopurinol to prevent developing hepatocellular carcinoma (HCC) and to explore the fundamental mechanisms that control the hepatoprotective effect considering the enormous impact of HCC on patients' quality of life. Male Sprague Dawely rats were given i.p.
View Article and Find Full Text PDFBr J Surg
November 2024
Centre of Research on Inflammation (CRI), INSERM U1149, Paris, France.
Therap Adv Gastroenterol
October 2024
Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
Cirrhotic liver nodules can progress to hepatocellular carcinoma (HCC) through a multi-step carcinogenesis model, with dysplastic nodules being particularly high risk. Currently, monitoring the progression of non-HCC cirrhotic nodules is primarily through dynamic observation, but there is a lack of sensitive, efficient, and convenient methods. Dynamic monitoring and risk evaluation of malignant transformation are essential for timely treatment and improved patient survival rates.
View Article and Find Full Text PDFJ Yeungnam Med Sci
October 2024
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Asian J Surg
October 2024
Second Ward of General Surgery, Gansu Province People Hospital, Lanzhou, 730000, China; The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China; Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Lanzhou, 730000, China; Gansu Engineering Research Center for Prevention and Control of Digestive Tract Malignancies, Lanzhou, 730000, China; Key Lab for Diagnosing and Treating Gastrointestinal Tumors, National Health and Welfare Commission, Lanzhou, 730000, China. Electronic address:
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