Project description:Colorectal cancer is a heterogeneous disease molecularly characterized by inherent genomic instabilities, chromosome instability and microsatellite instability. In the present study we propose transcriptome instability as an analogue to genomic instability on the transcriptome level. Exon microarray data from two independent series of altoghether 160 colorectal cancer tissue samples was used for global alternative splicing detection using the FIRMA algorithm (aroma.affymetrix). The sample-wise amounts of these alternative splicing scores exceeding a defined threshold (deviating exon usage amounts) were summarized to provide the basis for description of transcriptome instability. This characteristic was shown to be associated with splicing factor expression levels and patient survival in both independent sample series.
Project description:Colorectal cancer is a heterogeneous disease molecularly characterized by inherent genomic instabilities, chromosome instability and microsatellite instability. In the present study we propose transcriptome instability as an analogue to genomic instability on the transcriptome level. Exon microarray data from two independent series of altoghether 160 colorectal cancer tissue samples was used for global alternative splicing detection using the FIRMA algorithm (aroma.affymetrix). The sample-wise amounts of these alternative splicing scores exceeding a defined threshold (deviating exon usage amounts) were summarized to provide the basis for description of transcriptome instability. This characteristic was shown to be associated with splicing factor expression levels and patient survival in both independent sample series.
Project description:Colorectal cancer is a heterogeneous disease molecularly characterized by inherent genomic instabilities, chromosome instability and microsatellite instability. In the present study we propose transcriptome instability as an analogue to genomic instability on the transcriptome level. Exon microarray data from two independent series of altoghether 160 colorectal cancer tissue samples was used for global alternative splicing detection using the FIRMA algorithm (aroma.affymetrix). The sample-wise amounts of these alternative splicing scores exceeding a defined threshold (deviating exon usage amounts) were summarized to provide the basis for description of transcriptome instability. This characteristic was shown to be associated with splicing factor expression levels and patient survival in both independent sample series. We analyzed genome-wide expression at the exon-level for two independent series of colorectal cancer tissue biopsies using the Affymetrix Human Exon 1.0 ST platform. This series of samples represents the validation series.
Project description:Colorectal cancer is a heterogeneous disease molecularly characterized by inherent genomic instabilities, chromosome instability and microsatellite instability. In the present study we propose transcriptome instability as an analogue to genomic instability on the transcriptome level. Exon microarray data from two independent series of altoghether 160 colorectal cancer tissue samples was used for global alternative splicing detection using the FIRMA algorithm (aroma.affymetrix). The sample-wise amounts of these alternative splicing scores exceeding a defined threshold (deviating exon usage amounts) were summarized to provide the basis for description of transcriptome instability. This characteristic was shown to be associated with splicing factor expression levels and patient survival in both independent sample series. We analyzed genome-wide expression at the exon-level for two independent series of colorectal cancer tissue biopsies using the Affymetrix Human Exon 1.0 ST platform. This series of samples represents the test series.
Project description:Most proteogenomic approaches for mapping single amino acid polymorphisms (SAPs) require construction of a sample-specific database containing protein variants predicted from the next-generation sequencing (NGS) data. We present a new strategy for direct SAP detection without relying on NGS data. Among the 348 putative SAP peptides identified in an industrial yeast strain, 85.6% of SAP sites were validated by genomic sequencing.
Project description:HCT-116 cells were treated either with 5 µM of the NMD inhibitor 5-azacytidine (PMID: 25319547) or DMSO (negative solvent control) for 24 h to examine differences in HLA class I-mediated peptide presentation. Moreover, data were used for the identification of tumor-specific neoepitopes originating from insertion/deletion mutations due to microsatellite instability.
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: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.