Project description:Background/Aims: Microarray-based comparative genomic hybridisation (CGH) has allowed high-resolution analysis of DNA copy number alterations across the entire cancer genome. Recent advances in bioinformatics tools enable us to perform a robust and highly sensitive analysis of array CGH data and facilitate the discovery of novel cancer-related genes. Methods: We analysed a total of 29 pancreatic ductal adenocarcinoma (PDAC) samples (six cell lines and 23 microdissected tissue specimens) using 1 Mb-spaced CGH arrays. The transcript levels of all genes within the identified regions of genetic alterations were then screened using our Pancreatic Expression Database. Results: In addition to 238 high-level amplifications and 35 homozygous deletions, we identified 315 minimal common regions of “non-random” genetic alterations (115 gains and 200 losses) which were consistently observed across our tumour samples. The small size of these aberrations (median size of 880 kb) contributed to the reduced number of candidate genes included (on average 12 Ensembl-annotated genes). The database has further specified the genes whose expression levels are consistent with their copy number status. Such genes were UQCRB, SQLE, DDEF1, SLA, ERICH1 and DLC1, indicating that these may be potential target candidates within regions of aberrations. Conclusion: This study has revealed multiple novel regions that may indicate the locations of oncogenes or tumour suppressor genes in PDAC. Using the database, we provide a list of novel target genes whose altered DNA copy numbers could lead to significant changes in transcript levels in PDAC. (Harada et al. Pancreatology) Keywords: pancreatic ductal adenocarcinima, tissue microdissection, array CGH, genetic alterations
Project description:Background/Aims: Microarray-based comparative genomic hybridisation (CGH) has allowed high-resolution analysis of DNA copy number alterations across the entire cancer genome. Recent advances in bioinformatics tools enable us to perform a robust and highly sensitive analysis of array CGH data and facilitate the discovery of novel cancer-related genes. Methods: We analysed a total of 29 pancreatic ductal adenocarcinoma (PDAC) samples (six cell lines and 23 microdissected tissue specimens) using 1 Mb-spaced CGH arrays. The transcript levels of all genes within the identified regions of genetic alterations were then screened using our Pancreatic Expression Database. Results: In addition to 238 high-level amplifications and 35 homozygous deletions, we identified 315 minimal common regions of “non-random” genetic alterations (115 gains and 200 losses) which were consistently observed across our tumour samples. The small size of these aberrations (median size of 880 kb) contributed to the reduced number of candidate genes included (on average 12 Ensembl-annotated genes). The database has further specified the genes whose expression levels are consistent with their copy number status. Such genes were UQCRB, SQLE, DDEF1, SLA, ERICH1 and DLC1, indicating that these may be potential target candidates within regions of aberrations. Conclusion: This study has revealed multiple novel regions that may indicate the locations of oncogenes or tumour suppressor genes in PDAC. Using the database, we provide a list of novel target genes whose altered DNA copy numbers could lead to significant changes in transcript levels in PDAC. (Harada et al. Pancreatology) Keywords: pancreatic ductal adenocarcinima, tissue microdissection, array CGH, genetic alterations A panel of 23 microdissected PDAC tissues and 6 PDAC-derived cell lines were analysed using Sanger's CGH arrays with 1 Mb resolution. Clinical info of the samples used is provided as a supplementary file.
Project description:Establishment of a tumor bank, consisting of tissue samples of tumor patients (benign and malign tumors) and healthy people as controls. The tissue samples will be collected systematically together with the corresponding clinical data. The biological samples, the clinical date together with prospective experimental date constitute the entity of the tissue tumor bank.
This tumor bank for tissue samples, together with our tumorbank for blood samples (NCT01763125) combined constitute the entity "Tumorbank".
Project description:Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease with a 5 year overall survival rate of 11%. In order to better understand and characterized PDAC we have performed RNAseq on 289 primary and metastatic PDAC tumors collected at our center. Nucleic acids (RNA and DNA) were extracted from formalin fixed paraffin embeded FFPE tumor tissue with tumor enriched regions identified by pathologic analysis. RNA sequencing and resulting gene expression data was then used to study biologic differences in primary PDAC tumors that metastasized to either the liver or to the lung but not liver based on clinical data review. A novel gene expression signature was identified for liver vs lung avid metastatic properties. Samples in the entire cohort were then scored based on this gene signature. Pathway analysis revealed that samples high for this signature (as well as liver cohort patient samples) were enriched for pathways involved in ongoing replication stress response, and this was associated with poorer patient outcome.