Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors
Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Treatment options for patients with advanced‐stage disease are limited. A major obstacle in drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patien...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2019-07-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1365 |
| _version_ | 1797934786050785280 |
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| author | Tanja Blumer Isabel Fofana Matthias S. Matter Xueya Wang Hesam Montazeri Diego Calabrese Mairene Coto‐Llerena Tujana Boldanova Sandro Nuciforo Venkatesh Kancherla Luigi Tornillo Salvatore Piscuoglio Stefan Wieland Luigi M. Terracciano Charlotte K.Y. Ng Markus H. Heim |
| author_facet | Tanja Blumer Isabel Fofana Matthias S. Matter Xueya Wang Hesam Montazeri Diego Calabrese Mairene Coto‐Llerena Tujana Boldanova Sandro Nuciforo Venkatesh Kancherla Luigi Tornillo Salvatore Piscuoglio Stefan Wieland Luigi M. Terracciano Charlotte K.Y. Ng Markus H. Heim |
| author_sort | Tanja Blumer |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Treatment options for patients with advanced‐stage disease are limited. A major obstacle in drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patient‐derived xenograft (PDX) tumor mouse models could overcome the limitations of cancer cell lines. PDX tumors maintain the genetic and histologic heterogeneity of the originating tumors and are used for preclinical drug development in various cancers. Controversy exists about their genetic and molecular stability through serial passaging in mice. We aimed to establish PDX models from human HCC biopsies and to characterize their histologic and molecular stability during serial passaging. A total of 54 human HCC needle biopsies that were derived from patients with various underlying liver diseases and tumor stages were transplanted subcutaneously into immunodeficient, nonobese, diabetic/severe combined immunodeficiency gamma‐c mice; 11 successfully engrafted. All successfully transplanted HCCs were Edmondson grade III or IV. HCC PDX tumors retained the histopathologic, transcriptomic, and genomic characteristics of the original HCC biopsies over 6 generations of retransplantation. These characteristics included 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 approximately 20%. The transplanted tumors represent the entire spectrum of the molecular landscape of HCCs and preserve the characteristics of the originating tumors through serial passaging. HCC PDX models are a promising tool for preclinical personalized drug development. |
| first_indexed | 2024-04-10T18:04:23Z |
| format | Article |
| id | doaj.art-eae88299032b4b1a82fc109e9ddd17dc |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:04:23Z |
| publishDate | 2019-07-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-eae88299032b4b1a82fc109e9ddd17dc2023-02-02T14:09:16ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2019-07-013797198610.1002/hep4.1365Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating TumorsTanja Blumer0Isabel Fofana1Matthias S. Matter2Xueya Wang3Hesam Montazeri4Diego Calabrese5Mairene Coto‐Llerena6Tujana Boldanova7Sandro Nuciforo8Venkatesh Kancherla9Luigi Tornillo10Salvatore Piscuoglio11Stefan Wieland12Luigi M. Terracciano13Charlotte K.Y. Ng14Markus H. Heim15Department of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandInstitute of Pathology University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandInstitute of Pathology University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandInstitute of Pathology University Hospital Basel, University of Basel Basel SwitzerlandInstitute of Pathology University Hospital Basel, University of Basel Basel SwitzerlandInstitute of Pathology University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandInstitute of Pathology University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandDepartment of Biomedicine University Hospital Basel, University of Basel Basel SwitzerlandHepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Treatment options for patients with advanced‐stage disease are limited. A major obstacle in drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patient‐derived xenograft (PDX) tumor mouse models could overcome the limitations of cancer cell lines. PDX tumors maintain the genetic and histologic heterogeneity of the originating tumors and are used for preclinical drug development in various cancers. Controversy exists about their genetic and molecular stability through serial passaging in mice. We aimed to establish PDX models from human HCC biopsies and to characterize their histologic and molecular stability during serial passaging. A total of 54 human HCC needle biopsies that were derived from patients with various underlying liver diseases and tumor stages were transplanted subcutaneously into immunodeficient, nonobese, diabetic/severe combined immunodeficiency gamma‐c mice; 11 successfully engrafted. All successfully transplanted HCCs were Edmondson grade III or IV. HCC PDX tumors retained the histopathologic, transcriptomic, and genomic characteristics of the original HCC biopsies over 6 generations of retransplantation. These characteristics included 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 approximately 20%. The transplanted tumors represent the entire spectrum of the molecular landscape of HCCs and preserve the characteristics of the originating tumors through serial passaging. HCC PDX models are a promising tool for preclinical personalized drug development.https://doi.org/10.1002/hep4.1365 |
| spellingShingle | Tanja Blumer Isabel Fofana Matthias S. Matter Xueya Wang Hesam Montazeri Diego Calabrese Mairene Coto‐Llerena Tujana Boldanova Sandro Nuciforo Venkatesh Kancherla Luigi Tornillo Salvatore Piscuoglio Stefan Wieland Luigi M. Terracciano Charlotte K.Y. Ng Markus H. Heim Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors Hepatology Communications |
| title | Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors |
| title_full | Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors |
| title_fullStr | Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors |
| title_full_unstemmed | Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors |
| title_short | Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors |
| title_sort | hepatocellular carcinoma xenografts established from needle biopsies preserve the characteristics of the originating tumors |
| url | https://doi.org/10.1002/hep4.1365 |
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