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Series GSE115674 Query DataSets for GSE115674
Status Public on Jul 15, 2020
Title Genomic data from 48 Asian gastric patient-derived xenograft (PDX) models, 7 Asian gastric patient tumors and the 8 corresponding normal tissues
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary 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.
Overall design total DNA samples were extracted from one or two tumor samples per patient-derived xenograft model, one piece of normal patient tissue or one piece of patient tumor using a phenol:chloroform method. After standard quality controls DNA were subjected to Affymetrix GenomeWideSNP_6 microarray hybridization.
Contributor(s) Peille A, Vuaroqueaux V, Wong S, Ting J, Klinger K, Zeitouni B, Landesfeind M, Kim WH, Lee H, Kong S, Wulur I, Bray S, Bronsert P, Zanella N, Donoho G, Yang H, Fiebig H, Reinhard C, Aggarwal A
Citation(s) 32647357
Submission date Jun 12, 2018
Last update date Jul 15, 2020
Contact name Vincent Vuaroqueaux
Organization name 4HF Biotec
Department Bioinformatics
Street address Am Flughafen 14
City Freiburg
ZIP/Postal code 79108
Country Germany
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (62)
GSM3187458 GXA_3002 Type: Patient derived Xenograft Passage: 4
GSM3187459 GXA_3005 Type: Patient derived Xenograft Passage: 6; 3
GSM3187460 GXA_3011 Type: Patient derived Xenograft Passage: 3; 6N4
This SubSeries is part of SuperSeries:
GSE115755 Establishment of patient-derived tumor xenografts from Asian gastric adenocarcinoma is characterized by clonal selection and bias in molecular subtypes
BioProject PRJNA475762

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE115674_RAW.tar 1.7 Gb (http)(custom) TAR (of CEL)
GSE115674_processed_data.txt.gz 156.6 Kb (ftp)(http) TXT
Processed data are available on Series record

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