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. 2024 Oct;167(5):1029-1032.e7.
doi: 10.1053/j.gastro.2024.05.033. Epub 2024 Jun 10.

Human Hepatocytes Can Give Rise to Intrahepatic Cholangiocarcinomas

Bernadette Y Hsu  1 , Julia Driscoll  2 ; Human Cholangiocarcinogenesis Project; Chise Tateno  3 , Aras N Mattis  7 , Robin K Kelley  6 , Holger Willenbring  8
Collaborators, Affiliations

Human Hepatocytes Can Give Rise to Intrahepatic Cholangiocarcinomas

Bernadette Y Hsu et al. Gastroenterology. 2024 Oct.
No abstract available

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Conflict of interest statement

Conflicts of interest

These authors disclose the following: Chise Tateno and Yuji Ishida are employees of PhoenixBio Co, Ltd. The remaining authors disclose no conflicts.

Figures

Figure 1.
Figure 1.
Transformation of phHeps into iCCAs. (A–C) Photos of livers and spleens, H&E staining, and IHC of tumors from FRGN mice transplanted with phHeps transduced with lentiviral vectors expressing the indicated oncogene combinations, including tumor-type distribution. (D) Photos of livers and spleens, H&E staining, and IHC of tumors from FRGN mice transplanted with phHeps expressing the indicated oncogene combination and fed a DDC diet. Scale bars, 1 cm (photos) or 100 μm (H&E staining). (E) Heatmap of the 1000 genes most differentially expressed between phHep-derived iCCAs and UDCs and patient-derived iCCAs and HCCs. Tumors are color coded based on unsupervised clustering reflecting tumor type (iCCA vs HCC) and mutational profile for patient-derived tumors (letters) or oncogene combination (bold) and DDC diet for phHep-derived tumors (numbers) indicated by black boxes. Mutations and lentivirally expressed oncogenes are grouped based on association with oncogenic modules previously identified in patient iCCAs, including kinase signaling (HRAS-PTEN), cell cycle regulation and DNA damage and genomic instability (SV40Tt-TERT), SWItch/Sucrose Nonfermentable (ARID1A and ARID2) and de-ubiquitination (BAP1). (F) PCA comparing phHep-derived tumors with iCCAs and HCCs resected from patients at the University of California, San Francisco. Identifying numbers and letters are introduced in E. All phHep-derived tumors formed in FRGN mice except 40Tt;T;(H) iCCAs, which were derived from phHeps transduced with a low-efficiency HRAS-vector batch and transplanted into cDNA-uPA/SCID mice. (G) PCA comparing phHep-derived tumors with all iCCAs and corresponding nontumor tissue in TCGA-CHOL. 40Tt, SV40Tt; H, HRAS; NT, nontumor tissue; PC, principal component; T, TERT.
See this image and copyright information in PMC

References

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