Project description:Aim of the study was the distinction of adeoncarcinomas at the gastroesophageal junction by their expression profile. Differential gene expression analysis between tumours of different Siewert type did not reveal relevant results. Stratification into three intrinsic subgroups was done by an diagonal distribution model using the mclust package in R. Clinicopathological and demographic parameters showed a similar distribution within the subgroups. Genes set ernichment analysis revealed different biological features for each subgroup that were also reflected by significant differences in the prognostic outcome for the patients, mainly overall survival and recurrence free survival.
Project description:Aim of the study was the distinction of adeoncarcinomas at the gastroesophageal junction by their expression profile. Differential gene expression analysis between tumours of different Siewert type did not reveal relevant results. Stratification into three intrinsic subgroups was done by an diagonal distribution model using the mclust package in R. Clinicopathological and demographic parameters showed a similar distribution within the subgroups. Genes set ernichment analysis revealed different biological features for each subgroup that were also reflected by significant differences in the prognostic outcome for the patients, mainly overall survival and recurrence free survival.
Project description:Examine methylation changes in gene promoters in gastric cancers and matched normal control gastric epithelium, using Nimblegen arrays. Direct comparison of gastric cancers and matched normal control gastric epithelium
Project description:Gastric cancer is the second most common cause of cancer death worldwide, but incidence and mortality rates show large variations across different countries. Variation in risk factors between different populations, including environmental and host factors influencing gastric cancer risk, have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We set out to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA). DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis. Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p<0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p=0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK patients and Caucasian SA patients and between native and Caucasian SA patients. In conclusion, gastric cancers from South African and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms underlying the disease. 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients.
Project description:Examine methylation changes in gene promoters in gastric cancers and matched normal control gastric epithelium, using Nimblegen arrays.
Project description:Gastric cancer is the second most common cause of cancer death worldwide, but incidence and mortality rates show large variations across different countries. Variation in risk factors between different populations, including environmental and host factors influencing gastric cancer risk, have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We set out to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA). DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis. Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p<0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p=0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK patients and Caucasian SA patients and between native and Caucasian SA patients. In conclusion, gastric cancers from South African and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms underlying the disease.
Project description:Gene expression profiling of 273 pre-treatment endoscopic FFPE oesophageal and oesophago-gastric junctional adenocarcinomas for validation of a DNA Damage Response Deficiency Assay. All patients were treated with neo-adjuvant chemotherapy followed by surgical resection and were collected at four UK centres in the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium between 2004 and 2013. Biopsies were reviewed for pathological subtype prior to marking for macrodissection and samples containing at least 50% adenocarcinoma tissue by area were taken forward. Total RNA was extracted using the RecoverallTM Total Nucleic Acid Isolation Kit for FFPE (Thermo Fisher Scientific, Waltham, MA) and amplified using the NuGen Ovation FFPE Amplification System v3 (NuGen San Carlos, CA). The amplified product was hybridized to the Almac Diagnostics Xcel™ array (Almac, Craigavon, United Kingdom), a cDNA microarray-based technology optimized for archival FFPE tissue, and analysed using the Affymetrix 7G scanner (Affymetrix, Santa Clara, CA)