Project description:Here we report the RNA sequence of a primary patient-derived xenograft neuroendocrine tumor and compare it to the RNA sequence of an intraperitoneal metastatic tumor that was established using the respective primary tumor. Using this data, we identified key differences that validated the metastatic tumor to indeed have a more mestatic genotype. Noteworthy differences were the upregulation of matrix metalloproteinases and downregulation of PTK2, both associated with metastatic neuroendocrine tumors in patients. Furthermore, we found upregulated pathways that could potentially be targeted through small molecule inhibition. One such example is ERK1/2 had a higher expression in the metastatic tumor and using a MEK inhibitor, were able to successfully deplete metastasis of the tumor in an in vivo model. These data will be helpful in translating the therapeutics tested to a clinical arena.
Project description:Analysis of patient-derived xenograft cells at the basal level. A panel of T- and BCP-ALL pediatric leukaemia xenograft cells were utilised to further understand the biology of pediatric leukaemia. Total RNA were isolated from patient-derived xenograft cells. Illumina beadchip HT12 were utilised
Project description:Analysis of patient-derived xenograft cells at the basal level. A panel of T- and BCP-ALL pediatric leukaemia xenograft cells were utilised to further understand the biology of pediatric leukaemia.
Project description:Analysis of basal gene expression in patient-derived xenograft cells. A panel of pediatric T-, B- and MLL-ALL xenografts was utilized to further understand the biology of leukemia Total RNA was isolated from patient-derived xenograft cells. Array analysis was carried out on Illumina beadchip HT12
Project description:Analysis of basal gene expression in patient-derived xenograft cells. A panel of pediatric ALL xenografts was utilized to further understand the biology of leukemia.
Project description:Analysis of basal gene expression in patient-derived xenograft cells. A panel of pediatric T-, B- and MLL-ALL xenografts was utilized to further understand the biology of leukemia
Project description:Purpose: To define copy number alterations and gene expression signatures underlying pediatric high-grade glioma (HGG). Patients and Methods: We conducted a high-resolution analysis of genomic imbalances in 78 de novo pediatric HGG, including 7 diffuse intrinsic pontine gliomas, and 10 HGG cases arising in children who received cranial irradiation for a previous cancer, using Affymetrix 500K GeneChips. Gene expression signatures for 53 tumors were analyzed with Affymetrix U133v2 arrays. Results were compared with publicly available data from adult tumors. Results: Pediatric and adult glioblastoma were clearly distinguished by frequent gain of chromosome 1q (30% vs 9%) and lower frequency of chromosome 7 gain (13% vs 74%), respectively. The most common focal amplifications also differed, with PDGFRA and EGFR predominant in childhood and adult populations respectively. These common alterations in pediatric HGG were detected at higher frequency in irradiation-induced tumors, suggesting that these are initiating events in childhood gliomagenesis. CDKN2A was the most common tumor suppressor gene targeted by homozygous deletion in pediatric HGG. No IDH1 hotspot mutations were found in pediatric tumors, highlighting molecular differences in pathogenesis between childhood HGG and adult secondary glioblastoma. Integrated copy number and gene expression data indicated that deregulated PDGFRA signaling plays a major role in pediatric HGG. Conclusions: Integrated molecular profiling showed substantial differences in the molecular features underlying pediatric and adult HGG, indicating that findings in adult tumors cannot be simply extrapolated to younger patients. PDGFRA may be a useful target for pediatric HGG including diffuse pontine gliomas. Keywords: disease state analysis 78 samples for SNP analysis, including 10 samples arising in children who received cranial irradiation for a previous cancer and 7 diffuse pontine gliomas; 53 of them with gene expression analysis; 2 tumor grades To have access to SNP CEL files, please contact Dr. Suzanne Baker (suzzane.baker@stjude.org).