The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer

Krupke, Debra M.; Begley, Dale A.; Sundberg, John P.; Richardson, Joel E.; Neuhauser, Steven B.; Bult, Carol J.

doi:10.1158/0008-5472.can-17-0584

Cited by 59 publications

(65 citation statements)

References 14 publications

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“…Patient tumor engraftment and PDX passaging of various tumor types were performed as previously described 1–3 . Detailed information of the PDX models can be found in the PDX model search form in Mouse Tumor Biology Database (MTB, http://tumor.informatics.jax.org/mtbwi/pdxSearch.do).…”

Section: Methodsmentioning

confidence: 99%

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Woo¹,

Giordano

Srivastava³

et al. 2019

Preprint

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41 a PDXNET consortium 42 b EurOPDX consortium 43 # These authors contributed equally to this work.44 § These authors jointly supervised this work. ABSTRACT 107Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical 108 studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution 109 during PDX engraftment and propagation, impacting the accuracy of PDX modeling of human 110 cancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 PDX and matched 111 patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing 112 and microarray data displayed substantially higher resolution and dynamic range than gene 113 expression-based inferences, and they also showed strong CNA conservation from PTs through 114 late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-115 late trios confirmed high-resolution CNA retention. We observed no significant enrichment of 116 cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between 117 patient and PDX tumors were comparable to variations in multi-region samples within patients. 118Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse 119 host. 121 MAIN 122A variety of models of human cancer have been used to study basic biological processes and 123 predict responses to treatment. For example, mouse models with genetically engineered 124 mutations in oncogenes and tumor suppressor genes have clarified the genetic and molecular 125 basis of tumor initiation and progression 1,2 , though responses sometimes differ between human 126 and mouse 3 . Cell lines have also been widely used to study cancer cells, but they lack the 127 heterogeneity and microenvironment of in vivo tumors and have shown limitations for predicting 128 clinical response 4 . Human tumors engrafted into transplant-compliant recipient mice (patient-129 derived xenografts, PDX) have advantages over prior systems for preclinical drug efficacy studies 130 because they allow researchers to directly study human cells and tissues in vivo 5-8 . Comparisons131 of genome characteristics and histopathology of primary tumors and xenografts of human breast 132 cancer 9-13 , ovarian cancer 14 , colorectal cancer 15 and lung cancer 16-18 , have demonstrated that the 133 biological properties of patient-derived tumors are largely preserved in xenografts. A growing body 134 of literature supports their use in cancer drug discovery and development 19-21 . 135A caveat to PDX models is that intratumoral evolution can occur during engraftment and 136 passaging 11,22-25 . Such evolution could potentially modify treatment response of PDXs with 137 respect to the patient tumors 23,26,27 , particularly if the evolution were to systematically alter cancer-138 related genes. This issue is related to multi-region comparisons of patient tumors 28-31 , for which 139 local mutational and immune infiltration variations have sugg...

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Section: Methodsmentioning

confidence: 99%

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Woo¹,

Giordano

Srivastava³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

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“…5). [128][129][130] While they are useful for studying basic tumour biology, their use as a preclinical platform to evaluate the therapeutic response in HCC is still limited by the lack of systematic cross-species comparative molecular analyses. [131][132][133] New biomarkers While tumour tissue is still the gold standard source for identifying cancer-specific biomarkers, liquid biopsy has become a promising alternative non-invasive procedure, allowing for the isolation and detection of cancer-derived subcellular components that are released in biological fluids such as blood.…”

Section: Precision Oncology In Hccmentioning

confidence: 99%

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Rebouissou

Nault

2020

Journal of Hepatology

399

283

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Hepatocellular carcinoma (HCC) arises from hepatocytes through the sequential accumulation of multiple genomic and epigenomic alterations resulting from Darwinian selection. Genes from various signalling pathways such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase are frequently mutated in HCC. Several subclasses of HCC have been identified based on transcriptomic dysregulation and genetic alterations that are closely related to risk factors, pathological features and prognosis. Undoubtedly, integration of data obtained from both preclinical models and human studies can help to accelerate the identification of robust predictive biomarkers of response to targeted biotherapy and immunotherapy. The aim of this review is to describe the main advances in HCC in terms of molecular biology and to discuss how this knowledge could be used in clinical practice in the future.

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“…At the genomic level, engrafted human tumors have been shown to retain most genomic aberrations from the original patient tumor (8,10). These successes have led to the development of a number of PDX collections in both academia and industry (5,11,12) for use in preclinical testing.…”

Section: Introductionmentioning

confidence: 99%

Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis

et al. 2020

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receive a portion of royalties if University of Utah licenses certain PDX models to for-profit entities. M.T.L is a founder of, and equity stake holder in, Tvardi Therapeutics Inc., a founder of, and limited partner in, StemMed Ltd., and a Manager in StemMed Holdings LLC. He also receives a portion of royalties if Baylor College of Medicine licenses certain PDX models to for-profit entities. Research.

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The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer

Cited by 59 publications

References 14 publications

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis

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