Project description:Comparison of miRNA expression profiles in malignant germ cell tumors compared to non-malignant control group. Use of bioinformatic algorithm Sylamer to interrogate mRNA expression profiles from malignant germ cell tumors for enrichment or depletion of binding sites for differentially expressed miRNAs. Use of Gene Ontology (GO) analysis to demonstrate functional significance of differentially expressed miRNAs in malignant germ cell tumors. mRNA profiling: Analyzed global mRNA expresion profiles from 21 pediatric samples (17 malignant germ cell tumors, 1 benign germ cell tumor and 3 gonadal controls) using Sylamer (van Dongen et al, Nature Methods 2008, PMID 18978784) to study functional significance of differentially expressed miRNAs in malignant germ cell tumors. 16 of these files previously published - Palmer et al, Cancer Research 2008, PMID 18519683; GEO Accession Number GSE10615. Similarly, re-analyzed published global mRNA expresion profiles from 25 adult samples (20 malignant germ cell tumors and 5 testis controls) using Sylamer (van Dongen et al, Nature Methods 2008, PMID 18978784) to study functional significance of differentially expressed miRNAs in malignant germ cell tumors. These files previously published - Korkola at al, Cancer Research 2006, PMID 16424014; GEO Accession Number GSE3218. miRNA profiling: Analyzed global miRNA expression files from 48 samples including 32 pediatric gonadal and extragonadal germ cell tumors, 2 adult testicular seminomas, 8 gonadal and developmental control samples and 6 germ cell tumor cell lines. Re-analyzed published data (TaqMan MicroRNA Assays) from study of miRNA expression in adult gonadal germ cell tumors (Gillis et al, J Pathol 2007, PMID 17893849) and compared with pediatric findings. Re-analyzed data linked below as supplementary file.
Project description:Comparison of miRNA expression profiles in malignant germ cell tumors compared to non-malignant control group. Use of bioinformatic algorithm Sylamer to interrogate mRNA expression profiles from malignant germ cell tumors for enrichment or depletion of binding sites for differentially expressed miRNAs. Use of Gene Ontology (GO) analysis to demonstrate functional significance of differentially expressed miRNAs in malignant germ cell tumors.
Project description:Ovarian cancer is common among women. Cancer in ovaries can arise from three different tissues, epithelial, germ and stromal cells. Majority of ovarian cancer arise from epithelial tissues. However, cancer in the germ cells or stromal cells are histologically, genetically and clinically heterogeneous, which result in a challenge in terms of treatment. In this study, we generated sRNA libraries of germ cell tumors (7 benign and 2 malignant) as well as 3 stromal tumors. In particular, we analyzed the miRNA profile of these tumors and found that malignant ovarian germ cell tumors (OGCT) are genetically distinct from benign OGCT and sex cord-stromal tumors (SCST). We detected several miRNAs that were deregulated in malignant OGCT compared to benign and SCST and fewer deregulated miRNAs between benign OGCT and SCST. However, we were still able to detect several deregulated miRNAs between benign OGCT and SCST.
Project description:Testicular germ cell tumors are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse testicular germ cell tumor model in which germ cell-specific oncogenic Kras activation and tumor suppressor Pten inactivation was driven by CRE-mediated recombination. The resulting mice rapidly developed malignant, metastatic testicular cancers composed of both teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. As part of our analysis of mouse gPAK testicular tumors, as well as comparison to benign 129-Dnd1Ter/Ter testicular teratomas, we used NimbleGen Mouse CGH 3x720k Whole-Genome Tiling Arrays to assess copy number variations in this novel genetically engineered mouse model of malignant, metastatic testicular cancer.
Project description:Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or therapeutic applications. Examination of microRNA expression of cancer and matched adjacent tissues from 7 testicular germ cell tumors and 10 transitional cell carcinomas of bladder
Project description:Intracranial pediatric germ cell tumors (GCTs) have different histological differentiations, prognosis and clinical behaviors. Prognosis of patients with germinoma and mature teratoma is good, while patients with other types of GCTs, termed as nongerminomatous malignant germ cell tumors (NGMGCTs), require more extensive drug and irradiation treatment regimen. The mechanisms underlying different prognosis of various GCT subgroups remain elusive. We presented a distinct mRNA profile correlating with GCT histological differentiation and prognosis.
Project description:Background: USP8 mutations are the most common driver changes in corticotroph pituitary tumors. They have direct effect on cells’ proteome through disturbance of ubiquitination process and also influence gene expression. The aim of this study was to compare microRNA profiles in USP8- mutated and wild-type tumors and determine the probable role of differential microRNA expression by integrative microRNA and mRNA analysis. Methods: Patients with Cushing’s disease (n = 28) and silent corticotroph tumors (n = 20) were included. USP8 mutations were identified with Sanger sequencing. MicroRNA and gene expression was determined with next-generation sequencing. Results: USP8-mutated patients with Cushing’s disease showed higher rate of clinical remission and trend towards lower tumor volume than wild-type patients. Comparison of microRNA profiles of USP8-mutated and wild-type tumors revealed 68 differentially expressed microRNAs. Their target genes were determined by in silico prediction and microRNA/mRNA correlation analysis. GeneSet Enrichment analysis of putative targets showed that the most significantly overrepresented genes are involved in protein ubiquitination-related processes. Only few microRNAs influence the expression of genes differentially expressed between USP8-mutated and wild-type tumors. Conclusions: Differences in microRNA expression in corticotropinomas stratified according to USP8 status reflect disturbed ubiquitination processes, but do not correspond to differences in gene expression between these tumors.
Project description:To compare the transcriptome profiles of the two principal histological variants of malignant germ cell tumor that occur in childhood Experiment Overall Design: Here, we analyzed the global gene expression profiles of 27 pediatric MGCTs from the two principal histologies (18 yolk sac tumors [YSTs] and 9 seminomas).
Project description:Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or therapeutic applications. Examination of mRNA expression of cancer and matched adjacent tissues of 7 testicular germ cell tumors and 10 transitional cell carcinomas of bladder