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Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models

ABSTRACT: Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models

PROVIDER: PRJNA649229 | ENA |

REPOSITORIES: ENA

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Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models [RNA-seq]

Project description:Testicular cancer (TC) is the most common solid tumour in young men. While cisplatin-based chemotherapy is highly effective in TC patients, chemoresistance still accounts for 10% of disease-related deaths. Pre-clinical models that faithfully reflect patient tumours are needed to assist in target discovery and drug development. Tumour pieces from eight TC patients were subcutaneously implanted in NOD scid gamma (NSG) mice. Three patient-derived xenograft (PDX) models of TC, including one chemoresistant model, were established containing yolk sac tumour and teratoma components. Whole-exome sequencing, copy number variation analysis and RNA-sequencing was performed on these TP53 wild type PDX tumours to assess the effects of passaging, showing high concordance of molecular features between passages.

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Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models [SNP array]

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Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models [RNA-seq]

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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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Establishment and characterization of testicular cancer patient-derived xenograft (PDX) models

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

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Genomic data from 48 Asian gastric patient-derived xenograft (PDX) models, 7 Asian gastric patient tumors and the 8 corresponding normal tissues

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

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

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

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RNAseq analysis of SCLC PDX models

Project description:We investigated the gene expression changes in a library of small cell lung carcinoma (SCLC) patient-derived xenograft (PDX) models.

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