Differential Mutations In Matched Primary and Metastatic Colorectal Cancers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA314364 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:<p>This study compares DNA mutations detected in matched primary and metastatic colorectal cancer samples from 18 individuals across 1,321 genes. We found many more mutations were shared between tumor pairs (avg. 33.3 mutations/tumor) than were discordant (avg. 2.3 mutations / tumor). Nearly all tumors showed at least one discordance, and these were observed in genes known to be involved in colorectal cancer progression. Therefore, although primary and metastatic colorectal tumors are highly genetically concordant, evidence exists for discordance, which has clinical implications especially in situations of chemotherapy resistance or insensitivity.</p>
| phs001084 | dbGaP
Project description:Analysis of different proteomics profile in primary tumors of metastatic and non-metastatic breast cancers.
2023-03-09 | PXD037288 | Pride
Project description:Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients' tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER + BC is highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth in multiple endocrine and palbociclib resistant PDX. Mutations in the PIK3CA/AKT1 genes are significantly associated with response to IACS-010759. At the metabolic level, in vivo response to IACS-010759 is associated with decreased levels of metabolites of the glutathione, glycogen and pentose phosphate pathways in treated tumours. In vitro, endocrine and palbociclib resistant cells show increased OXPHOS dependency and increased ROS levels upon IACS-010759 treatment. Finally, in ER + BC patients, high expression of OXPHOS associated genes predict poor prognosis. In conclusion, these results identify OXPHOS as a promising target for treatment resistant ER + BC patients.
2023-06-27 | MTBLS3342 | MetaboLights
Project description:Characterization of patterns of somatic alterations between matched primary and metastatic colorectal tumors using whole genome sequencing technology
| PRJEB4388 | ENA
Project description:Differential Mutations In Matched Primary and Metastatic Colorectal Cancers
| PRJNA314365 | ENA
Project description:We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis. We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss (SCNAs). The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar SCNA patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number of alterations. Genomically, colorectal and metastatic liver tumors were very similar. However, in a subgroup of patients, there were genetic variations in liver metastases in the loss of DNA mismatch repair genes. Copy number analysis of Affymetrix CytoScanHD arrays was performed for 15 primary colorectal carcinoma and 15 samples of their matched liver metastases. 15 normal samples prepared from each of the patient was used as the reference for the study. Nexus Copy number 6.1 software was used for somatic copy number alteration analysis.
2014-03-01 | E-GEOD-53799 | biostudies-arrayexpress
Project description:19 non-metastatic breast cancers (controls) and 19 breast cancers showing metastases or metastatic relapse within 5 years (cases) were extracted from a multi-institutional case series of 123 breast cancer patients . Cases and controls were analyzed for DNA methylation over 56 genes by the MethDet assay [1]using a dedicated microarray (MethDet56). 1. Levenson VV, Melnikov AA: The MethDet: a technology for biomarker development. Expert Rev Mol Diagn 2011, 11:807-812.
2015-03-20 | E-MTAB-3153 | biostudies-arrayexpress
Project description:We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis. We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss (SCNAs). The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar SCNA patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number of alterations. Genomically, colorectal and metastatic liver tumors were very similar. However, in a subgroup of patients, there were genetic variations in liver metastases in the loss of DNA mismatch repair genes.
2014-03-01 | GSE53799 | GEO
Project description:Copy number analyses of regionally separated biopsies from primary and metastatic lesions of five colorectal cancers A total of 35 intratumoral biopsies were obtained from primary and metastatic lesions of five colorectal cancers. Board-certified pathologists reviewed the hematoxylin&eosin stained sections and identified tumor-rich regions (> 80% purity) to ensure minimal contamination of normal tissues. We selected two to six different areas for biopsy that were at least 5mm apart in primary and distant metastatic lesions from a same patient. Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol. The genomic DNA obtained from the adjacent normal tissues were used as reference genomic DNA for the tumor DNA of the corresponding patients.
2014-06-16 | E-GEOD-58512 | biostudies-arrayexpress
Project description:To look at genes/pathways differentially expressed in metastatic and primary tumor cells we performed global gene expression profiling of the 3 sets of HNSCC lines derived from primary tumors and matched metastatic sites. Illumina HT-12 v4 BeadChip arrays were used. The data suggest that HNSCC lines derived from metastatic sites exhibit phenotypes distinct from those found in cells derived from the corresponding primary tumors. Metastatic cell lines upregulated several pathways involved in stem cell self-renewal, invasion and migration, which are well known characteristics of metastatic progression. We conclude that the cell lines derived from primary patient tumors and matched metastatic sites represent a reliable model to study HNSCC metastasis.
2018-07-27 | GSE117753 | GEO