Field effect of healthy and diseased livers
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001002382 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Recent work in the Campbell group has revealed somatic mutations present in normal, non-cancerous human skin. A subset of the mutations conferred selective advantages to the host cells, leading to clonal expansions and raising the risk for future cancer development. Capturing such somatic mutations in normal tissue is important to advance our understanding about carcinogenesis and could provide prospective medical insights.
In this project, our goal is to detect somatic mutations in normal (pre-cancerous) liver tissue. Using Laser Microdissection technology, we will dissect individual liver lobules from patient samples and submit these to sequencing. For each patient sample, we aim to sequence multiple lobules to characterise the mutagenic burden. Samples will be taken from patients with different liver disease aetiologies, including alcoholism and obesity, with a view on distinguishing the prevalent mutation types occurring in each disease context.
We will perform both whole genome and targeted sequencing, initially using the WTSI cancer panel. Later we aim to use a novel bait set that captures both cancer genes as well as genes relevant to the non-cancerous samples (ie. genes implicated in hereditary disorders, immune sequences).
| EGAS00001002413 | EGA
Project description:Recent work in the Campbell group has revealed somatic mutations present in normal, non-cancerous human skin. A subset of the mutations conferred selective advantages to the host cells, leading to clonal expansions and raising the risk for future cancer development. Capturing such somatic mutations in normal tissue is important to advance our understanding about carcinogenesis and could provide prospective medical insights.
In this project, our goal is to detect somatic mutations in normal (pre-cancerous) liver tissue. Using Laser Microdissection technology, we will dissect individual liver lobules from patient samples and submit these to sequencing. For each patient sample, we aim to sequence multiple lobules to characterise the mutagenic burden. Samples will be taken from patients with different liver disease aetiologies, including alcoholism and obesity, with a view on distinguishing the prevalent mutation types occurring in each disease context.
We will perform targeted sequencing, initially using the WTSI cancer panel. Later we aim to use a novel bait set that captures both cancer genes as well as genes relevant to the non-cancerous samples (ie. genes implicated in hereditary disorders, immune sequences).
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This dataset contains all the data available for this study on 2019-04-08.
| EGAD00001004941 | EGA
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:<p>Molecular profiling for somatic mutations that predict response to anti-EGFR therapy in colorectal cancer (CRC) has become standard practice. However, abundant tissue from metastatic lesions is not always available from patients with metastatic CRC. Concerns involving genetic heterogeneity between primary and metastatic lesions have called into question the suitability of profiling primary tumors in patients with metastatic disease. Further, the identification of discordant mutations between matched primary and metastatic tumors would be of biological interest for the delineation of biomarkers of tumor progression and metastasis.</p> <p>To explore the degree of genetic heterogeneity between matched primary and metastatic tumors in CRC, we performed whole genome sequencing of four patient "trios" comprised of a primary colon tumor, a liver metastasis, and matched normal (non-cancerous) tissue. Somatic mutations and indels were called in each tumor and compared between primary and metastatic lesions.</p>
| phs000790 | dbGaP
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:The aim of this study is to compare post-Hepatitis C (HCV) and post-Alcoholism (ALC) Hepatocellular Carcinoma gene expression profiling. Owing to transcriptome analysis with a cDNA array virtually covering every transcript in liver, we compared tumors vs paired cirrhosis or tumors vs controls as a function of etiology, i.e. alcoholism (ALC) vs hepatitis C virus (HCV). The so-called Significance Analysis of Microarray was used to identify those genes with the most informative changes in transcript levels. Comparisons of tumor/cirrhosis ratios or tumor/controls ratios between 12 alcoholic vs 10 HCV patients identified a total of 31 transcripts whose altered ratios appropriately clustered the patients according to etiology. Keywords: etiology analysis
2005-11-19 | GSE3632 | GEO
Project description:Orton2009 - Modelling cancerous mutations in
the EGFR/ERK pathway - EGF Model
This model studies the aberrations in
ERK signalling for different cancer mutations. The authors alter a
previously existing EGF model (Brown et al 2004) to include new
interactions that better fit empirical data.
Predictions show that the ERK signalling is a robust mechanism
taking different courses for different cancer mutations. Most
parameter values are used from the previous model and the new
parameters are estimated using experimental data performed by
the authors on PC12 cells (adrenal gland, rat). The authors
provide an SBML version of the model in the paper.
This model is described in the article:
Computational
modelling of cancerous mutations in the EGFR/ERK signalling
pathway.
Orton RJ, Adriaens ME, Gormand A,
Sturm OE, Kolch W, Gilbert DR.
BMC Syst Biol 2009 Oct; 3: 100
Abstract:
The Epidermal Growth Factor Receptor (EGFR) activated
Extracellular-signal Regulated Kinase (ERK) pathway is a
critical cell signalling pathway that relays the signal for a
cell to proliferate from the plasma membrane to the nucleus.
Deregulation of the EGFR/ERK pathway due to alterations
affecting the expression or function of a number of pathway
components has long been associated with numerous forms of
cancer. Under normal conditions, Epidermal Growth Factor (EGF)
stimulates a rapid but transient activation of ERK as the
signal is rapidly shutdown. Whereas, under cancerous mutation
conditions the ERK signal cannot be shutdown and is sustained
resulting in the constitutive activation of ERK and continual
cell proliferation. In this study, we have used computational
modelling techniques to investigate what effects various
cancerous alterations have on the signalling flow through the
ERK pathway.We have generated a new model of the EGFR activated
ERK pathway, which was verified by our own experimental data.
We then altered our model to represent various cancerous
situations such as Ras, B-Raf and EGFR mutations, as well as
EGFR overexpression. Analysis of the models showed that
different cancerous situations resulted in different signalling
patterns through the ERK pathway, especially when compared to
the normal EGF signal pattern. Our model predicts that
cancerous EGFR mutation and overexpression signals almost
exclusively via the Rap1 pathway, predicting that this pathway
is the best target for drugs. Furthermore, our model also
highlights the importance of receptor degradation in normal and
cancerous EGFR signalling, and suggests that receptor
degradation is a key difference between the signalling from the
EGF and Nerve Growth Factor (NGF) receptors.Our results suggest
that different routes to ERK activation are being utilised in
different cancerous situations which therefore has interesting
implications for drug selection strategies. We also conducted a
comparison of the critical differences between signalling from
different growth factor receptors (namely EGFR, mutated EGFR,
NGF, and Insulin) with our results suggesting the difference
between the systems are large scale and can be attributed to
the presence/absence of entire pathways rather than subtle
difference in individual rate constants between the
systems.
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2024-09-02 | BIOMD0000000623 | BioModels
Project description:Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that in many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. We analyzed 16 tissue samples from four patients. For each patient we analyzed the DNA of a primary colon tumor sample, a normal colon tissue sample, a metastatic liver tumor sample and a normal liver tissue sample. The normal colon and normal liver samples serve as a control for the primary and metastatic tumor samples.
2011-10-11 | E-GEOD-32711 | biostudies-arrayexpress
Project description:It is still unclear whether hepatic stellate cells (HSC) activate in a similar manner in different chronic liver disease aetiologies. Here, we investigate how human stellate cells activate in vitro at the transcriptome level.
2024-10-25 | GSE276915 | GEO