Journal
CANCER CELL
Volume 35, Issue 6, Pages 932-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.04.007
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Funding
- NCC Research Fund of Singapore [NCCRF-YR2014-Jan-PG2]
- Scientific Research Seed Fund of PKUFH [2018SF039]
- JSPS KAKENHI [18H04049]
- National Key Research and Development Program [2016YFC0900102]
- National Science and Technology Major Project [2018ZX10302205]
- Guangdong Province Key Research and Development Program [2019B020226002]
- National Natural Science Foundation of China [81802813, 81520108022, 81830090, 81661128009, 31671421, 81472683]
- Grants-in-Aid for Scientific Research [18H04049] Funding Source: KAKEN
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We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC.
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