Genomics

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Hepatocellular carcinoma xenografts established from needle biopsies preserve the characteristics of the originating tumors


ABSTRACT: Background & Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide with limited treatment options for patients with advanced stage disease. A major obstacle in preclinical drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patient derived xenograft (PDX) mouse models could overcome the limitations of cancer cell lines. PDX models have been established from surgically resected HCCs. We aimed to establish and characterize PDX models from human HCC biopsies in order to expand the spectrum of HCC xenografts to advanced HCCs not amenable to surgery. Methods: Fifty-four human HCC needle biopsies were transplanted subcutaneously into immunodeficient NOD-SCID gamma-c (NSG) mice. Tumor growth rates, histopathological characteristics, RNA sequencing and whole exome sequencing were used to characterize the newly established mouse models and to compare them to the originating HCCs. Results: Eleven HCCs engrafted in NSG mice. They were derived from patients with various underlying liver diseases and tumor stages. All successfully transplanted HCCs were Edmondson grade III or IV. HCC PDX tumors retained the histopathological, transcriptomic and genomic characteristics of the original HCC biopsies over several generations of re-transplantation, including Edmondson grade, expression of tumor markers, tumor gene signature, tumor-associated mutations and copy number alterations. Conclusion: PDX mouse models can be established from undifferentiated HCCs with an overall success rate of about 20%. The transplanted tumors represent the entire spectrum of the molecular landscape of HCCs and preserve the characteristics of the originating tumors. HCC PDX models are a promising tool for preclinical personalized drug development.

PROVIDER: EGAS00001003396 | EGA |

REPOSITORIES: EGA

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