Comparative genomics research for Chinese colorectal cancer
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ABSTRACT:
PROVIDER: EGAS00001002607 | EGA |
REPOSITORIES: EGA
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Project description:In order to clarify the mechanisms of genesis and development of colorectal carcinoma, in this study, we performed comparative genomics research in Chinese colorectal cancer at various clinical stage via whole exon sequencing or whole genome sequencing. Comparative bioinformatical analysis was perform to find the difference on somatic single-nucleotide variants, short insert/deletion variants, genomic structural variants, and copy number variants between cancer tissue and normal tissue, or among cancer tissues at various clinical stages.
| EGAS00001002576 | EGA
Project description:Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these aberrations harbour one or few genes. The aim of this study is to identify recurrent focal chromosomal aberrations and their candidate driver genes in a well defined series of stage II colon cancers and assess their potential clinical relevance. High resolution DNA copy number profiles were obtained from 38 formalin fixed paraffin embedded colon cancer samples with matched normal mucosa as a reference using array comparative genomic hybridization. In total, 81 focal chromosomal aberrations were identified that harboured 177 genes. Statistical validation of focal aberrations and identification of candidate driver genes was performed by enrichment analysis and mapping copy number and mutation data of colorectal-, breast-, pancreatic cancer and glioblastomas to loci of focal aberrations in stage II colon cancer. This analysis demonstrated a significant overlap with previously identified focal amplifications in colorectal cancer, but not with cancers from other sites. In contrast, focal deletions seem less tumour type specific since they also show significant overlap with focal deletions of other sites. Focal deletions detected are significantly enriched for cancer genes and genes frequently mutated in colorectal cancer. The mRNA expression of these genes is significantly correlated with DNA copy number status, supporting the relevance of focal aberrations. Loss of 5q34 and gain of 13q22.1 were identified as independent prognostic factors of survival in this series of patients. In conclusion, focal chromosomal copy number aberrations in stage II colon cancer are enriched in cancer genes which contribute to and drive the process of colorectal cancer development. DNA copy number status of these genes correlate with mRNA expression and some are associated with clinical outcome. 38 Stage II colorectal cancer (CRC) tissue samples (FFPE) of which 19 were done on expression arrays. One sample (Stage II colorectal cancer tissue samples (FFPE) 26) was also done on the 135K NimbleGen array. Fresh frozen and FFPE of the same CRC stage I sample was done on 105K agilent. The fresh frozen was across array in silico set out against a pool of blood of 18 healthy females.
2010-04-19 | E-GEOD-17047 | biostudies-arrayexpress
Project description:PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) of the expressed genes between these two groups. To characterize the clinical relevance of two highly-ranked differentially expressed signature genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.035), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p < 0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p < 0.0001) and LEF1 overexpression (p < 0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among signature genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 31 freshly-frozen primary colorectal cancer specimens, and compared to published profiles of 32 unmatched colorectal liver metastases and 12 normal liver specimens.
2011-03-22 | E-GEOD-22834 | biostudies-arrayexpress
Project description:Migrating cancer stem cells (MCSCs) are believed to be tumorigenic initiators of metastasis. However, the relevance of MCSCs for organ-specific metastasis in colorectal cancer remains unclear. Using in vivo selection, transcriptomic analysis and functional verification, we cultured colorectal cancer stem cells and discovered specific cell surface markers of MCSCs exhibiting distinct abilities to metastasize to the liver and lung. These results have important clinical implications as selection criterion for post-operative adjuvant therapy. The human primary colorectal cancer cells from colorectal cancer patient (CRC102) were orthotopically injected into NOG mice. The cancer cells in the liver or lung metastases were orthotopically injected into a new set of mice. After six selection cycles, we obtained cancer cells that produce spontaneous liver (CRC102LM) or lung metastases (CRC102PM). Under serum-free conditions, all individual cells produced nonadherent, multicellular oncospheres. Total RNA extracted from oncospheres of organ-specific metastasizing variants and their parental cells was used to generate biotinylated complementary RNA (cRNA) by following the standard Agilent GeneChip protocol.
2013-05-30 | E-GEOD-47467 | biostudies-arrayexpress
Project description:Migrating cancer stem cells (MCSCs) are believed to be tumorigenic initiators of metastasis. However, the relevance of MCSCs for organ-specific metastasis in colorectal cancer remains unclear. Using in vivo selection, transcriptomic analysis and functional verification, we cultured colorectal cancer stem cells and discovered specific cell surface markers of MCSCs exhibiting distinct abilities to metastasize to the liver and lung. These results have important clinical implications as selection criterion for post-operative adjuvant therapy. The human primary colorectal cancer cells from colorectal cancer patient (CRC105) were orthotopically injected into NOG mice. The cancer cells in the liver or lung metastases were orthotopically injected into a new set of mice. After six selection cycles, we obtained cancer cells that produce spontaneous liver (CRC105LM) or lung metastases (CRC105PM). Under serum-free conditions, all individual cells produced nonadherent, multicellular oncospheres. Total RNA extracted from oncospheres of organ-specific metastasizing variants and their parental cells was used to generate biotinylated complementary RNA (cRNA) by following the standard Agilent GeneChip protocol.
2013-05-30 | E-GEOD-47468 | biostudies-arrayexpress
Project description:Migrating cancer stem cells (MCSCs) are believed to be tumorigenic initiators of metastasis. However, the relevance of MCSCs for organ-specific metastasis in colorectal cancer remains unclear. Using in vivo selection, transcriptomic analysis and functional verification, we cultured colorectal cancer stem cells and discovered specific cell surface markers of MCSCs exhibiting distinct abilities to metastasize to the liver and lung. These results have important clinical implications as selection criterion for post-operative adjuvant therapy. The human primary colorectal cancer cells from colorectal cancer patient (CRC108) were orthotopically injected into NOG mice. The cancer cells in the liver or lung metastases were orthotopically injected into a new set of mice. After six selection cycles, we obtained cancer cells that produce spontaneous liver (CRC108LM) or lung metastases (CRC108PM). Under serum-free conditions, all individual cells produced nonadherent, multicellular oncospheres. Total RNA extracted from oncospheres of organ-specific metastasizing variants and their parental cells was used to generate biotinylated complementary RNA (cRNA) by following the standard Agilent GeneChip protocol.
2013-05-30 | E-GEOD-47469 | biostudies-arrayexpress
Project description:BRAF mutant colorectal cancer has a poor prognosis and gets resistant to BRAF inhibitors quickly. This study aims to clarify the mechanism of resistance to BRAFi. We found MCU1-C is overexpressed in BRAF mutant colorectal cancer and targeting MUC1-C genetically and pharmacologically sensitized Colorectal cancer cells to BRAF inhibitor. This finding suggests that MUC1-C could be a new therapeutic target for BRAF mutant colorectal cancer.
2022-11-30 | GSE215849 | GEO
Project description:We conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy. Patients accessible to tumor biopsy were prospectively enrolled at the Paoli-Calmettes Institute in the PERMED01 study (ClinicalTrials.gov, NCT02342158). Genomic profiling of frozen tissue was established by whole-genome array comparative genomic hybridization (aCGH)
2021-03-01 | E-MTAB-9998 | biostudies-arrayexpress
Project description:Only about 25% of familial breast cancer is explained by mutations in BRCA1 and BRCA2, fewer by moderate penetrance genes like P53, PTEN, CHEK2, ATM and PALB2 and an unknown fraction by common variants of genes with low penetrance. Evidence suggests that additional dominant breast cancer genes exist and these are referred to as BRCAX. Clinical presentation of families with highly increased incidence of breast cancer that are non-BRCA1/BRCA2, suggests dominant inheritance of such high penetrance breast cancer genes. Because cancer genes often confer a specific clinical presentation (e.g. age of onset, sex-ratio, tissue spectrum) it seems useful to initiate their discovery by such clinical criteria. An earlier linkage study of BRCAX / non-BRCA1/2 breast cancer families aimed to enrich for a common genetic defect by setting stringent inclusion criteria, failed to identify new breast cancer susceptibility loci. Motivated by results of BRCA1 and BRCA2 breast tumors that have characteristic genomic signatures (array-CGH 'phenotypes'), we present the largest dataset to date showing the genomic profiles of 58 BRCAX primary breast tumors by array-CGH and show by unsupervised hierarchical clustering that they form a heterogeneous group with 4 distinct subtypes that are different from (n = 48) sporadic controls. This provides a possible explanation for the lack of high LOD scores in linkage studies. The presence of more than one BRCAX sub-type suggests the existence of more than one BRCAX gene. We propose approaches that can be employed to stratify BRCAX families based on array-CGH data. 58 primary breast carcinomas from non-BRCA1/2 hereditary breast cancer families (HBC) compared to 48 sporadic tumors
2011-02-01 | E-GEOD-18626 | biostudies-arrayexpress
Project description:Wnt signaling plays important roles in development and cancer. We found hiNOS is a wnt target gene. We tried to clarify the role of the so far iNOS in Wnt signaling in colorectal cancer.
2013-08-20 | GSE50009 | GEO