Project description:We investigated the gene expression changes in a library of small cell lung carcinoma (SCLC) patient-derived xenograft (PDX) models.
Project description:RNAseq was done on Breast cancer PDX samples uisng Library protocol =llumina TruSeq Stranded Total RNA Kit with Ribo-Zero Gold , HiSeq 125 Cycle Paired-End Sequencing v4
Project description:Purpose: Study the changes in the transcriptome of metastatic melanoma PDX cells upon combination treatment with AURKA and MEK inhibitors Methods: RNAseq analysis of melanoma PDX cells treated with AURKA inhibitor Alisertib (500nM) and MEK inhibitor trametinib (100nM) for 72 h
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.
Project description:RNA-Seq and a species-specific mapping strategy were used to profile the human and mouse transcriptomes of tumour samples taken from 79 PDX models representing multiple cancer types (19 x breast, 37 x lung, 8 x colorectal, 7 x ovarian, 3 x endometrial, 2 x pancreatic, 2 x ampullary, 1 x leukaemia).
Project description:A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at genomic level to identify new therapeutic targets associated with endocrine resistance in the metastatic setting. Identification of chromosomic alterations in bone metastasis derived PDX.
