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Establishment of Gastric Cancer Patient-derived Xenograft Models and Primary Cell Lines
Published on: July 19, 2019
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Deciphering Cancer Evolution Through Genomic Profiling of Patient-Derived Xenograft Together with Matched Primary
Vipin Yadav1, Ragini Kilambi2, Archana Rastogi3
1Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
Digestive Diseases and Sciences
|November 9, 2025
Summary
A patient-derived xenograft (PDX) model of gallbladder adenosquamous carcinoma was established. This model, driven by KRAS (G12V) mutation, aids in studying tumor evolution and identifying potential cancer stem cells.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Gallbladder cancer exhibits poor prognosis due to late detection and aggressive nature.
- Adenosquamous subtypes are rare and molecularly undercharacterized.
- Patient-derived xenograft (PDX) models are valuable for studying tumor heterogeneity and evolution.
Purpose of the Study:
- To establish and characterize a PDX model for gallbladder adenosquamous carcinoma.
- To investigate tumor progression and cellular origin using longitudinal specimens.
- To identify key molecular drivers and evolutionary patterns in gallbladder cancer.
Main Methods:
- Established a PDX model from a patient's metastatic gallbladder cancer lesion.
- Utilized immunohistochemistry (IHC) to assess marker expression in primary, metastatic, and PDX tumors.
- Employed targeted next-generation sequencing (NGS) to analyze clonal evolution and genomic alterations.
Main Results:
- The PDX model successfully recapitulated the histopathological and marker features of the original tumors.
- KRAS (G12V) was identified as the primary oncogenic driver, with additional mutations (PIK3CA, LRP1B) emerging in later stages.
- Genomic analysis revealed acquisition of mutations in chromatin remodeling genes (ARID2, ARID1A, BAP1) in the PDX model, indicating adaptive selection.
- Clonal trajectory analysis demonstrated both branched and linear evolution patterns.
Conclusions:
- A functional PDX model for gallbladder adenosquamous carcinoma was successfully generated.
- KRAS (G12V) is a potential initiating mutation, and EpCAM-positive cells are likely tumor-initiating cancer stem cells.
- The PDX model revealed the emergence of resistant clones and adaptive selection of chromatin remodelers during tumor progression.
Keywords:
Adenosquamous carcinomaClonal evolutionGenetic landscapePatient-derived xenograftPrognostic markerMore Related Videos
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