E-MTAB-5008 - Methylation profiling by array of pancreatic adenocarcinoma (PDAC) xenografts
Released on 12 December 2017, last updated on 27 September 2018
Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. the variable MultiOmicsClassification indicates the resulting sample's group. Whole-genome DNA methylation was analyzed using the Illumina Infinium HumanMethylation450 Beadchips. Integragen SA (Evry, France) carried out microarray experiments and hybridized to the BeadChip arrays following the manufacturer’s instructions. Illumina GenomeStudio software was used to extract the beta value DNA methylation score for each locus. We removed data from probes that contained SNPs or overlapped with a repetitive element that was not uniquely aligned to the human genome or regions of insertions and deletions in the human genome. The CpG Island Methylator Phenotype (CIMP) index was determined using methylation Illumina Infinium HumanMethylation450 BeadChips based on previous low throughput work (Toyota, 1999). In brief, all island CpG found to be unmethylated (<20% Beta-value) in all 25 normal pancreatic samples from the ICGC consortium (Nones, 2014) were selected. The CIMP index was calculated independently for each sample as the proportion of methylated (>30% Beta-value) CpGs among the selected normally unmethylated island CpG.
methylation profiling by array, genotype design
Multiomics characterization of Patients-Derived pancreatic cancer Xenografts. R. Nicolle, Y. Blum, L. Marisa, N. Dusetti, J. Iovanna.