Whole-genome expression analysis of melanoma tumor biopsies from a population-based cohort
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jönsson Göran
PROVIDER: S-ECPF-GEOD-65904 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Analysis of gene expression profiles in metastatic melanoma to validate prognostic signatures.
2015-04-01 | GSE65904 | GEO
Project description:Analysis of gene expression profiles in metastatic melanoma to validate prognostic signatures. Total RNA was extracted from fresh-frozen melanoma tumors and genome-wide expression profiling was performed using Illlumina Human HT-12V4.0 BeadChip arrays by standard methods. After removal of replicate samples there were 214 unique melanoma samples left.
2015-04-01 | E-GEOD-65904 | biostudies-arrayexpress
Project description:The immune system recognizes diverse melanoma antigens. However, tumors can evade the immune response, therefore growing and progressing. It has been reported that galectin-3 and galectin-1 can induce apoptosis of activated lymphocytes. However, there is strong evidence indicating that the regulation of galectins function in the human tumor microenvironment is a complex process that is influenced by diverse biological circumstances. Here, we have investigated 33 biopsies (eight primary and 25 metastases) from 24 melanoma patients (15-72 years old) and describe the correlation between the expression of galectin-3 or galectin-1 and the level of apoptosis of tumor-associated lymphocytes using immunohistochemistry and an in situ nick translation assay. The range of galectin-3-positive tumor cells varied between 0% and 93% and that of galectin-1-positive tumor cells varied between 5% and 97%. In addition, 23 +/- 27% of tumor-associated lymphocytes were apoptotic. Although our results show a correlation between galectin-3 expression and apoptosis of tumor-associated lymphocytes, we could not find such correlation with galectin-1. Considering the complex process of cancer immunoediting, various interacting factors must be considered.
| S-EPMC1606586 | biostudies-literature
Project description:Previous genome-wide expression studies have highlighted distinct gene expression patterns in inflammatory bowel disease (IBD) compared to control samples, but the interpretation of these studies has been limited by sample heterogeneity with respect to disease phenotype, disease activity, and anatomic sites. To further improve molecular classification of inflammatory bowel disease phenotypes we focused on a single anatomic site, the disease unaffected proximal ileal margin of resected ileum, and three phenotypes that were unlikely to overlap: ileal Crohn's disease (ileal CD), ulcerative colitis (UC), and control patients without IBD. Whole human genome (Agilent) expression profiling was conducted on two independent sets of disease-unaffected ileal samples collected from the proximal margin of resected ileum. Set 1 (47 ileal CD, 27 UC, and 25 Control non-IBD patients) was used as the training set and Set 2 was subsequently collected as an independent test set (10 ileal CD, 10 UC, and 10 control non-IBD patients). We compared the 17 gene signatures selected by four different feature-selection methods to distinguish ileal CD phenotype with non-CD phenotype. The four methods yielded different but overlapping solutions that were highly discriminating. All four of these methods selected FOLH1 as a common feature. This gene is an established biomarker for prostate cancer, but has not previously been associated with Crohn's disease. Immunohistochemical staining confirmed increased expression of FOLH1 in the ileal epithelium. These results provide evidence for convergent molecular abnormalities in the macroscopically disease unaffected proximal margin of resected ileum from ileal CD subjects.
| S-EPMC3351422 | biostudies-literature
Project description:In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.
| S-EPMC10063166 | biostudies-literature
Project description:Aberrant DNA methylation and histone modifications both contribute to carcinogenesis, but how these two epigenetic factors interact to impact gene expression remain unclear. To address this issue, we studied gene expression profiles, DNA methylation and two key histone modifications (H3K4me3 and H3K27me3), in two normal melanocytes (HEMn and HEMa) and two melanoma cell lines SK-MEL-28 and LOXIMVI. Using these data, we analyzed the relationship between epigenetic factors and gene expression status in both normal and melanoma cells, and the impact of epigenetic switches on gene expression change during melanomagenesis. Each of the two normal melanocytes (HEMn and HEMa) and the two melanoma cell lines SK-MEL-28 and LOXIMVI was cultured in triplicate. For each cell line, the same culture conditions and cell density were applied to the triplicates. Total RNA was extracted and microarray analysis was performed for genome-wide gene expression profiling. Using the Sentrix Human-HT12 v4 Beadchip, all four cell samples, each in triplicate, were examined in 12 individual arrays on a same beadchip. Thus, together with the data on DNA methylation and histone modifications, we could not only analyze the epigenetic regulation of gene expression in each cell sample, but also investigate the expression change associated with epigenetic changes in melanoma when compared to normal melanocytes.
| S-ECPF-GEOD-31909 | biostudies-other
Project description:Sentinel lymph node, the first node draining the primary tumor, is a key component of tumor microenvironment promoting immune tolerance. In melanoma, sentinel node is one of the most important prognostic factors and the most frequent site of regional metastasis. To unravel the immunomodulatory pathways that are triggered by melanoma cells in the draining node that allow tumor spreading, transcriptional profiles associated to disease progression were analyzed in archival sentinel node biopsies (SNB). Gene expression profiles of melanoma-positive and negative SNB selected to maximize the differences in terms of disease stage and course, revealed subgroups correlating with regional node involvement and disease progression within positive biopsies. Transcriptional profiles revealed that genes showing differential expression between tumor-positive SNB with/without disease progression were mainly related to inflammatory response and that were mostly down regulated in patients with poor prognosis. TNFRSF8 encoding CD30 showing up regulation in SNB from patients with progressing disease displayed higher expression by immunohistochemical staining compared to SNB from non progressing patients. Subpopulations of CD30 positive CD4/CD8 double negative and CD4 Foxp3/PD-1 CD147 positive T cells were identified by flow cytometry analysis in metastatic nodes, suggesting a potential role of regulatory and tolerogenic T cells in melanoma progression. Cutaneous melanoma patients undergoing SNB biopsy in 2001-2004 with available 5–year follow-up clinical data were selected. Data relative to 752 cases was extracted, 80% (n= 603) with a negative SNB and 20% (n=149) with SNB positivity for melanoma metastases. The latter underwent regional lymphadenectomy by CLND and 30% (n=44) resulted positive for melanoma metastases at non-sentinel regional lymph nodes while 70% (n=105) resulted negative. Analysis of follow-up data showed that disease recurrence at 5 yrs occurred in 9% SNB negative patients, 14% of the patients with positive SNB resulting negative at CLND, and in 57% of the patients with positive SNB resulting positive at CLND, consistent to the range of previously reported rates (Santinami M 2009, Balch CM 2009). In order to exploit gene expression profiles to unravel molecular modifications occurring in SNB from patients with progressing disease we selected two groups of cases representing the extremes of the survey, i.e. patients positive at CLND (stage IIIB-C) recurring within 5 years follow-up (SNB-PP), and patients negative at CLND (stage IIIA-B) and non-relapsing at 5 years (SNB-PN). In addition, a group of negative SNB patients without disease recurrence at 5 years was selected and analysed for comparison as tumor negative SNB (SNB-N).
| S-ECPF-GEOD-39945 | biostudies-other
Project description:SummaryFragmentation patterns of cell-free DNA reflect the chromatin structure of the cells from which these fragments are derived. Nucleosomes protect the DNA from fragmentation, resulting in decreased sequencing coverage in regions of open chromatin. LIQUORICE is a user-friendly software tool that takes aligned whole-genome sequencing data as input and calculates bias-corrected coverage signatures for predefined, application-specific sets of genomic regions. The tool thereby enables a blood-based analysis of cell death in the body, and it provides a minimally invasive assessment of tumor chromatin states and cell-of-origin. With user-defined sets of regions that exhibit tissue-specific or disease-specific open chromatin, LIQUORICE can be applied to a wide range of detection, classification and quantification tasks in the analysis of liquid biopsies.Availability and implementationLIQUORICE is freely and openly available as a Python package and command-line tool for UNIX-based systems from bioconda. Documentation, examples and usage instructions are provided at http://liquorice.computational-epigenetics.org.Supplementary informationSupplementary data are available at Bioinformatics Advances online.
| S-EPMC9710688 | biostudies-literature
Project description:Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ? 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.
| S-EPMC4792591 | biostudies-literature
Project description:Cancer stem cells (CSCs) represent a small subpopulation of tumor cells that play a critical role in initiating and sustaining tumor growth. However, we currently have an incomplete understanding of the expression patterns of CSC antigens in tumors of dogs, nor do we understand how expression of these antigens vary between tumor cell lines and tumor biopsy specimens. Therefore, we used flow cytometry and commonly reported CSC surface and intracellular markers to evaluate the phenotype and overall frequency of CSC subpopulations in tumor cell lines and primary tumor biopsy samples from dogs with melanoma and osteosarcoma. We found that cells expressing common CSC antigens were rare in tumor cell lines, with the exception of tumor cells expressing CD44 and CD90. In contrast, tumor cells expressing conventional CSC antigens such as CD133, CD34, CD44, CD24 and Oct3/4 were much more common in tumor biopsy samples. Notably, the frequency and types of putative CSC subpopulations were very similar in biopsy samples from dogs with either melanoma or osteosarcoma. Our results suggest that the tumor microenvironment significantly influences CSC subpopulations within tumors and that tumor cell lines may not accurately reflect the actual frequency or types of CSC subpopulations present in tumor tissues in vivo.
| S-EPMC4264625 | biostudies-literature