Project description:Patient derived xenografts (PDXs) of human EGFR-mutant lung cancer were propagated in mice and treated with osimertinib or control to investigate the transcriptional adaption resposne.
Project description:Patient-derived tumor xenografts (PDXs) increasingly are being used as preclinical models to study human cancers and to evaluate novel therapeutics, as they reflect clinical cancers more closely than established tumor cell lines. With >100 PDXs established from resected non-small cell lung carcinomas (NSCLC), we reported previously that xenograftability correlates significantly with poorer patient prognosis. In this study, genomic, transcriptomic, and proteomic profiling of 36 PDXs showed greater similarity in somatic alterations between PDX and primary tumors than with cell lines, using publicly available data on the latter. A higher number of somatic alterations among 865 frequently altered genes in the PDX tumors was associated with better overall patient survival (HR=0.15, p=0.00015) compared to patients with corresponding PDXs characterized by a lower number of alterations; this was validated with the TCGA lung cancer patient dataset (HR=0.28, p=0.000022). These passenger-like alterations, identified in PDXs, link cell-cell signaling and adhesion to patient prognosis. Total RNAs from xenograftswere amplified by DASL kit and hybridized to Illumina HT12v4 chip
Project description:We generated patient cSCC-derived xenografts (cSCC-PDXs) that recapitulate the histopathologic and molecular features of parental patient samples. Response to gefitinib treatment was tested in four independent models. cSCC34-PDXs showed intrinsic resistance to gefitinib, whereas three models (cSCC10-PDXs, cSCC16-PDXs and cSCC24-PDXs) initially showed a strong response to gefitinib, but acquired resistance after long-term treatment. RNA sequencing analysis were performed in matched untreated and gefitinib-resistant cSCC-PDXs to determine mechanisms behind gefitinib resistance.
Project description:Epigenomics has identified methylated gene regions that are specific for colorectal cancer (CRC). Through Epigenomics’ marker discovery and validation process Septin 9 was identified as a particularly robust methylation marker for detection of CRC. Epigenomics is currently developing a blood based CRC screening test based on Septin 9 and is performing a large prospective clinical trial showing its clinical utility in a population at average risk for CRC. Parallel to this trial further activities are needed to evaluate, optimize, and develop pre-analytical and analytical workflows as well as molecular assays making possible the use of Septin 9 methylation in the clinical routine.
Project description:Epigenomics is developing a colon cancer screening assay based on differential methylation of specific CpG sites for the detection of early stage disease. A genome-wide methylation analysis and oligonucleotide array study using DNA from various stages of colon cancer and normal tissue have been completed to obtain candidate CpG markers. Based on results obtained in the above studies, Epigenomics has moved to the final stages of feasibility with a specific, highly sensitive real-time marker assay that is able to detect colon cancer DNA in blood plasma.
