Friemel, Juliane; Torres, Irianna; Brauneis, Elizabeth; Thörner, Tim; Schäffer, Alejandro A; Gertz, E Michael; Grob, Tobias; Seidl, Kati; Weber, Achim; Ried, Thomas; Heselmeyer-Haddad, Kerstin (2022). Single-cell resolved ploidy and chromosomal aberrations in nonalcoholic steatohepatitis-(NASH) induced hepatocellular carcinoma and its precursor lesions. Scientific reports, 12(1), p. 22622. Springer Nature 10.1038/s41598-022-27173-z
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Nonalcoholic steatohepatitis (NASH)-induced hepatocellular carcinoma (HCC) and its precursor, nonalcoholic fatty liver disease (NAFLD) are an unmet health issue due to widespread obesity. We assessed copy number changes of genes associated with hepatocarcinogenesis and oxidative pathways at a single-cell level. Eleven patients with NASH-HCC and 11 patients with NAFLD were included. Eight probes were analyzed using multiplex interphase fluorescence in situ hybridization (miFISH), single-cell imaging and phylogenetic tree modelling: Telomerase reverse transcriptase (TERT), C-Myc (MYC), hepatocyte growth factor receptor tyrosine kinase (MET), tumor protein 53 (TP53), cyclin D1 (CCND1), human epidermal growth factor receptor 2 (HER2), the fragile histidine triad gene (FHIT) and FRA16D oxidoreductase (WWOX). Each NASH-HCC tumor had up to 14 distinct clonal signal patterns indicating multiclonality, which correlated with high tumor grade. Changes frequently observed were TP53 losses, 45%; MYC gains, 36%; WWOX losses, 36%; and HER2 gains, 18%. Whole-genome duplications were frequent (82%) with aberrant tetraploid cells evolving from diploid ancestors. Non-tumorous NAFLD/NASH biopsies did not harbor clonal copy number changes. Fine mapping of NASH-HCC using single-cell multiplex FISH shows that branched tumor evolution involves genome duplication and that multiclonality increases with tumor grade. The loss of oxidoreductase WWOX and HER2 gains could be potentially associated with NASH-induced hepatocellular carcinoma.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology |
UniBE Contributor: |
Friemel, Juliane, Grob, Tobias |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
05 Jan 2023 14:58 |
Last Modified: |
08 Jan 2023 02:11 |
Publisher DOI: |
10.1038/s41598-022-27173-z |
PubMed ID: |
36587184 |
BORIS DOI: |
10.48350/176729 |
URI: |
https://boris.unibe.ch/id/eprint/176729 |
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