48c91c3e-29f2-47f1-a45e-14fbd3af1a20 - samples
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PROVIDER: EGAD00001008476 | EGA |
REPOSITORIES: EGA
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Project description:Background: Hodgkin lymphoma (HL) and testicular cancer (TC) survivors have an increased risk of developing second primary bowel malignancies (both colorectal cancer (CRC) and small bowel adenocarcinoma (SBA)). We aimed to determine differences in genetic characteristics of second primary bowel malignancies and primary bowel malignancies.
Methods: Copy number aberrations (CNAs) generated by low-coverage whole-genome sequencing (WGS) were collected from previous studies of second primary CRC (HL survivors, n=39), primary CRC (n=90) and primary SBA (n=14). In addition, seven new samples of second primary SBA from HL (n=3) or TC (n=5) survivors, identified in the Dutch national pathology registry (PALGA), were available for low-coverage WGS.
Results: Overall, CNA patterns observed in second primary bowel malignancies were similar to those in primary bowel malignancies. Losses of 21q22.2 were observed more frequently (p=0.057) in second primary CRC compared with primary CRC, while in second primary SBA gains of 10p15.3-15.1 and losses of 18q12.1-23 were significantly more frequent detected compared with primary SBA.
Conclusions: Second primary CRC and SBA show comparable genome wide CNAs to those in primary CRC and SBA, respectively. This suggests that part of the pathogenesis of second primary tumours in these cancer survivors is similar to those of primary CRC and SBA in general, despite the exposure to DNA damaging treatments received for earlier HL and TC.
| EGAS00001005940 | EGA
Project description:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor.
2014-02-10 | GSE38479 | GEO
Project description:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor. In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (liver, lung, ovarian, omentum and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH).
2014-02-10 | E-GEOD-38479 | biostudies-arrayexpress
Project description:Human colorectal cancer (CRC) cell lines are a used widely-used to model system for investigation investigate of tumour biology, experimental therapytherapeutic and biomarkers discovery. However, to what extent these established CRC cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we analyzed 70 CRC cell lines were analysed for mutations using whole exome sequencing and DNA copy-number using by whole-exome sequencing and SNP microarray profilings, respectively. Presence of gGene expression was defined using RNA-Seq. Data from cellCell line datas were was compared to those that published from for primary CRCs published by in The the Cancer Genome Atlas Network. Notably, we found that The spectrum of exome mutations and DNA copy-number aberrations spectra in 70 CRC cell lines closely resembled those seen inat of primary colorectal tumours. Similarities included the presence of at least two hypermutation phenotypes, as defined by signatures of for defective DNA mismatch repair and DNA polymerase ? (POLE) proof-reading deficiency, and along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGF? and p53 pathways. In additionFurther, we documented mutations were enriched in genes involved in chromatin remodelling (ARID1A, CHD6, SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, TRRAP). Chromosomal instability was prevalent in non-hypermutated cases, with similar patterns of whole, partial and focal chromosomal aberrations and overlapping significant minimal regions ofchromosomal gains and losses. While paired cell lines derived from the same tumour were found to exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differenceslargely mainly reflected a pre-existing heterogeneity in the tumour cells heterogeneity. In conclusion, our results establish that human CRC lines are representative of the main subtypes of primary tumours at the genomic level, further validating underscoring their utility as tools for to investigating investigate CRC biology and drug responses. 69 colorectal cancer cell lines were analysed for DNA copy number profiles.
2015-04-09 | E-GEOD-55832 | biostudies-arrayexpress
Project description:To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations.
2019-02-05 | GSE126053 | GEO
Project description:Human colorectal cancer (CRC) cell lines are a used widely-used to model system for investigation investigate of tumour biology, experimental therapytherapeutic and biomarkers discovery. However, to what extent these established CRC cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we analyzed 70 CRC cell lines were analysed for mutations using whole exome sequencing and DNA copy-number using by whole-exome sequencing and SNP microarray profilings, respectively. Presence of gGene expression was defined using RNA-Seq. Data from cellCell line datas were was compared to those that published from for primary CRCs published by in The the Cancer Genome Atlas Network. Notably, we found that The spectrum of exome mutations and DNA copy-number aberrations spectra in 70 CRC cell lines closely resembled those seen inat of primary colorectal tumours. Similarities included the presence of at least two hypermutation phenotypes, as defined by signatures of for defective DNA mismatch repair and DNA polymerase ε (POLE) proof-reading deficiency, and along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGFβ and p53 pathways. In additionFurther, we documented mutations were enriched in genes involved in chromatin remodelling (ARID1A, CHD6, SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, TRRAP). Chromosomal instability was prevalent in non-hypermutated cases, with similar patterns of whole, partial and focal chromosomal aberrations and overlapping significant minimal regions ofchromosomal gains and losses. While paired cell lines derived from the same tumour were found to exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differenceslargely mainly reflected a pre-existing heterogeneity in the tumour cells heterogeneity. In conclusion, our results establish that human CRC lines are representative of the main subtypes of primary tumours at the genomic level, further validating underscoring their utility as tools for to investigating investigate CRC biology and drug responses.
2015-04-09 | GSE55832 | GEO
Project description:Purpose: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently the number of clinical trials has been very limited due to the small numbers of patients. Chemotherapy regimens are currently rather arbitrarily chosen between either a colorectal (CRC) or a gastric cancer (GC) regimen. Chromosomal copy number aberrations are a hallmark of solid tumours and can be measured by array comparative genomic hybridization (aCGH). The aim of the present study is to investigate whether genome-wide copy number aberrations of SBA are more similar to CRC or GC in order to support treatment of SBA according to either regimen. Experimental Design: A total of 85 GCs, CRCs and SBAs were selected from existing in house aCGH datasets based on array quality and clinical parameters. Differences and similarities in gains and losses of the three tumor types were analyzed using supervised and unsupervised analysis. Results: Hierarchical clustering revealed substantial overlap of chromosomal copy number profiles between SBA and CRC and less overlap between SBA and GC. Chromosome 13q13.2-q31.3 is primarily gained in SBA and CRC and the strongest feature discriminating SBA from GC. Further strong discriminating copy number characteristics are aberrations at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1 and 17p13.3-p13.2. Conclusions: SBA is more similar to CRC than to GC, based on genome-wide copy number aberrations. These data provide molecular support for treatment of SBA according to a CRC regimen.
2011-06-13 | GSE23418 | GEO
Project description:Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumor biology. Here we describe the genomic landscape of tumor samples of a homogeneous well-annotated series of patients with metastatic CRC of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal sub-regions are associated with progression free survival PFS (uncorrected single-test p-values < 0.005). These sub-regions are filtered for effect on mRNA expression, using an independent data set from The Cancer Genome Atlas (TCGA) which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of metastatic CRC reveals a number of DNA copy number aberrations associated with response to drug therapy.
2014-11-14 | GSE36864 | GEO
Project description:Purpose: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently the number of clinical trials has been very limited due to the small numbers of patients. Chemotherapy regimens are currently rather arbitrarily chosen between either a colorectal (CRC) or a gastric cancer (GC) regimen. Chromosomal copy number aberrations are a hallmark of solid tumours and can be measured by array comparative genomic hybridization (aCGH). The aim of the present study is to investigate whether genome-wide copy number aberrations of SBA are more similar to CRC or GC in order to support treatment of SBA according to either regimen. Experimental Design: A total of 85 GCs, CRCs and SBAs were selected from existing in house aCGH datasets based on array quality and clinical parameters. Differences and similarities in gains and losses of the three tumor types were analyzed using supervised and unsupervised analysis. Results: Hierarchical clustering revealed substantial overlap of chromosomal copy number profiles between SBA and CRC and less overlap between SBA and GC. Chromosome 13q13.2-q31.3 is primarily gained in SBA and CRC and the strongest feature discriminating SBA from GC. Further strong discriminating copy number characteristics are aberrations at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1 and 17p13.3-p13.2. Conclusions: SBA is more similar to CRC than to GC, based on genome-wide copy number aberrations. These data provide molecular support for treatment of SBA according to a CRC regimen. 29 gastric adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control samples, 29 colorectal adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control, 27 small bowel adenocarcinomas done on 30K oligonucleotide arrays of which 2 samples are also done on 5K BAC arrays as control.
2011-06-13 | E-GEOD-23418 | biostudies-arrayexpress
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