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Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer [RNA-seq]

ABSTRACT: Transcriptome levels of matched patient-derived xenograft (PDX) in vitro-in vivo models.

OTHER RELATED OMICS DATASETS IN: PRJNA432416PRJNA432417PRJNA432411

ORGANISM(S): Homo sapiens

PROVIDER: GSE109903 | GEO | 2018/01/31

REPOSITORIES: GEO

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Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer [WES]

Project description:Whole exome sequencing of matched patient-derived xenograft in vitro-in vivo models.

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Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:We have generated a collection of patient-derived xenograft (PDX) tumor models and characterized them at the molecular level to facilitate precision oncology. Surgically resected HCC specimens were subcutaneously implanted in immunodeficient mice. Resulting xenografts were serially implanted to establish transplantable PDX models, which were sequentially subject to whole exome sequencing (WES), gene expression array, genome-wide human single nucleotide polymorphism (SNP) array 6.0, and serum a–fetoprotein (AFP) detection assay. The feasibility as a preclinical model was validated by efficacy studies using a standard-of-care (SOC) and a targeted agent, respectively.

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Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer

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| PRJNA432411 | ENA

Expression data from 27 Asian gastric patient-derived xenograft (PDX) models

Project description:There is a strong need to develop patient-derived xenograft (PDX) tumor models for studying new treatment options for gastric cancer (GC). With low engraftment success, few collections of GC PDX have been reported and molecular basis of the model establishment remain largely unknown. Here we established n=27 PDX models from n=100 GC tumors and compared their characteristics to GC patient tumors based on the recent work done by ACRG and TCGA, to evaluate the representativeness and relevance of the collection for drug testing. We show that MSI, CIN and MSS/TP53- tumors were preferentially established as PDX, while MSS/EMT and EBV not and that PDX models retained histology and molecular subtypes of parental tumors. By using synapse database, we identified 48 druggable alterations that could be investigated with the collection. Counting alterations for these 48 genes in PDX compared to TCGA tumors revealed models frequently classified with heavily altered tumors but well preserved genomic alteration patterns specific of each GC subtype. The molecular analysis of n=8/27 tumors and corresponding PDX at passage P1, P2 and P3 revealed variations in somatic alteration content both at single nucleotide and chromosomal level in highly unstable MSI and CIN tumors, with changes occurring mainly at P1. In two cases, we show likely emergence of rare subclones carrying known oncogenic alterations in KRAS and PIK3CA. Significance. This study presents a resource of fully annotated GC PDX models for anticancer agent testing. We show that beside close resemblance of PDX with parental tumors, not all subtypes are established, and that the clonal selection plays a key role the establishment of certain tumors. This may have a bearing on translation of observations into the clinic and underline the need to frequently survey the molecular characteristics of the PDX models.

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Whole transcriptome profiling of 79 patient derived xenograft (PDX) models

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