Copy number analysis of recurrent metastatic melanoma lesions
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38137 | GEO | 2013/12/31
SECONDARY ACCESSION(S): PRJNA167382
REPOSITORIES: GEO
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Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution.
2013-12-31 | GSE38119 | GEO
Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution. Twenty-six recurrent melanoma metastases were surgically isolated from 8 patients experiencing relapse after one or more successful treatment intervention(s) with no signs of residual disease. Patients experiencing recurrent metastases were labeled with capital letters; M-bM-^@M-^\AM-bM-^@M-^], M-bM-^@M-^\BM-bM-^@M-^], M-bM-^@M-^\CM-bM-^@M-^], etc., their subsequent metastases as M-bM-^@M-^\A/1M-bM-^@M-^], M-bM-^@M-^\A/2M-bM-^@M-^], M-bM-^@M-^\B/1M-bM-^@M-^], M-bM-^@M-^\B/2M-bM-^@M-^], etc., while synchronous metastases in a given patient were labeled as M-bM-^@M-^\A/1aM-bM-^@M-^], M-bM-^@M-^\A/1bM-bM-^@M-^] etc. Another 22 melanoma cell lines isolated and maintained as above were expanded from melanoma patients with rapid disease curse, for whom only one metastasis was available. As no extended follow up was possible in these cases, the cell lines are considered representative of random time points in the natural course of metastatic melanoma. These cell lines were labeled with Arabic numbers, as M-bM-^@M-^\1M-bM-^@M-^], M-bM-^@M-^\2M-bM-^@M-^], M-bM-^@M-^]3M-bM-^@M-^], etc
2013-12-31 | E-GEOD-38119 | biostudies-arrayexpress
Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution. Twenty-six recurrent melanoma metastases were surgically isolated from 8 patients experiencing relapse after one or more successful treatment intervention(s) with no signs of residual disease. Patients experiencing recurrent metastases were labeled with capital letters; M-bM-^@M-^\AM-bM-^@M-^], M-bM-^@M-^\BM-bM-^@M-^], M-bM-^@M-^\CM-bM-^@M-^], etc., their subsequent metastases as M-bM-^@M-^\A/1M-bM-^@M-^], M-bM-^@M-^\A/2M-bM-^@M-^], M-bM-^@M-^\B/1M-bM-^@M-^], M-bM-^@M-^\B/2M-bM-^@M-^], etc., while synchronous metastases in a given patient were labeled as M-bM-^@M-^\A/1aM-bM-^@M-^], M-bM-^@M-^\A/1bM-bM-^@M-^] etc. Another 22 melanoma cell lines isolated and maintained as above were expanded from melanoma patients with rapid disease curse, for whom only one metastasis was available. As no extended follow up was possible in these cases, the cell lines are considered representative of random time points in the natural course of metastatic melanoma. These cell lines were labeled with Arabic numbers, as M-bM-^@M-^\1M-bM-^@M-^], M-bM-^@M-^\2M-bM-^@M-^], M-bM-^@M-^]3M-bM-^@M-^], etc.
2013-12-31 | E-GEOD-38137 | biostudies-arrayexpress
Project description:Melanoma recurrence frequently occurs after a latency period of several years. In vivo studies demonstrated that tumor cells overcoming latency show a T cell-edited phenotype, suggesting a relevant role for CD8+ T cells in maintaining metastatic latency. Here, in a patient model of multiple recurrent lesions, we illustrate the genetic evolution of poorly immunogenic melanoma phenotypes, evolving in the presence of autologous tumor antigen-specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. HLA class I-negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed total T-cell resistance in both metastases originating from a shared chromosome 15q alteration and independently acquired focal B2M gene deletions. A third HLA class I-positive lesion developed in year 3 of stage IV disease. By HLA haplotype loss lesion-derived melanoma cells acquired resistance towards dominant T-cell clonotypes targeting early stage III tumor cells. Early disease melanoma cells showed a dedifferentiated MITFnegative phenotype, recently described to be associated with immunosuppression, in contrast to the MITFhigh phenotype of T cell-edited tumor cells from late metastases. In summary, our study demonstrates that tumor recurrences after long-term latency develop towards T-cell resistance by independent genetic events, suggesting a mechanism of T cell-driven genetic evolution of melanoma as a means to evade immune recognition and tumor immunotherapy. Genetic alterations lead to loss of tumor antigen presentation. Cell lines were generated from tumor material, differences in T cell recognition were observed and Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from the cell lines. SNP analysis of different melanoma cell lines obtained from one melanoma patient (4 cell lines from different metastasis of one patient with matching germline DNA).
2016-07-27 | E-GEOD-80736 | biostudies-arrayexpress
Project description:Melanoma recurrence frequently occurs after a latency period of several years. In vivo studies demonstrated that tumor cells overcoming latency show a T cell-edited phenotype, suggesting a relevant role for CD8+ T cells in maintaining metastatic latency. Here, in a patient model of multiple recurrent lesions, we illustrate the genetic evolution of poorly immunogenic melanoma phenotypes, evolving in the presence of autologous tumor antigen-specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. HLA class I-negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed total T-cell resistance in both metastases originating from a shared chromosome 15q alteration and independently acquired focal B2M gene deletions. A third HLA class I-positive lesion developed in year 3 of stage IV disease. By HLA haplotype loss lesion-derived melanoma cells acquired resistance towards dominant T-cell clonotypes targeting early stage III tumor cells. Early disease melanoma cells showed a dedifferentiated MITFnegative phenotype, recently described to be associated with immunosuppression, in contrast to the MITFhigh phenotype of T cell-edited tumor cells from late metastases. In summary, our study demonstrates that tumor recurrences after long-term latency develop towards T-cell resistance by independent genetic events, suggesting a mechanism of T cell-driven genetic evolution of melanoma as a means to evade immune recognition and tumor immunotherapy. Genetic alterations lead to loss of tumor antigen presentation.
2016-07-27 | GSE80736 | GEO
Project description:Brain metastases of melanoma are associated with therapy resistance and poor prognosis. It is not fully understood whether and how the selection of cells capable of metastasizing into the brain is accompanied by the establishment of specific features. For the investigation of these questions, we made use of previously described xenograft mouse models for primary human melanoma cells distinguishing cutaneous from cerebellar metastases from the same genetic background. Previous experiments suggested that cultured cells derived from these xenografts still maintain properties characteristic for the microenvironment of the originating metastases. Such corresponding pairs of metastatic cells were obtained from four individual donors, resulting in eight cell-lines presently investigated with regard to molecular properties characteristic for metastasis. Label free proteome profiling revealed significant alterations when comparing corresponding pairs of cutaneous and cerebellar metastases from the same donor. Molecules previously associated with metastasis such as cell adhesion molecules, immune regulators, epithelial mesenchymal transition markers, stem cell markers, redox regulators and cytokines were found differently expressed. This was also observed with regard to eicosanoids considered relevant for metastasis such as PGE2 and 12-HETE. However, no commonalities in the molecular characteristics of cerebellar metastases were identified in all four donors. Multiparametric morphological analysis of cells also revealed alterations associated with the kind of metastases, while lacking uniformity. In conclusion, here we describe that xenografted melanoma cells derived from two different microenvironments, i.e. cutaneous and cerebellar metastases, display significant alterations in the expression of molecules associated with metastastic properties. The observed lack of uniformity suggests that metastatic cells may find individual strategies to adapt to their microenvironmental challenges accompanied by the establishment of individual cell characteristics.
2020-01-08 | PXD013765 | Pride
Project description:Circulating tumor cells (CTCs) are critical in the development of distant organ tumor metastasis, and are associated with advanced cancer stage and poor patient outcome. Here, we present the first genome-wide nucleotide-level characterization of CTCs. Our single-nucleotide polymorphism (SNP) analysis in patients with melanoma involved: 1) global comparative genomic analysis of CTCs and matched regional metastases, 2) identification of key genomic aberrations in CTCs, 3) verification of these target genes in aggressive distant tumor metastases, and 4) evidence of selective expression and functional consequence of CTC-associated genes in melanomas. We report 131 aberrant loci in CTCs that are potentially pro-metastatic, and show that such expression of a 5-marker gene panel (CSMD2, CNTNAP5, FLJ14051, ADAM6, TRPM2) in melanomas confers prognostic utility. Successful treatment of melanoma requires understanding of the metastatic process and identification of patients with tumors most likely to develop aggressive metastatic disease. Melanomas are heterogeneous, and CTCs have long been recognized as vehicles for cancer spread, representing particularly aggressive tumor clones that can evolve into successful clinical metastases. Elucidation of genomic aberrations in CTCs will aid in the development of prognostic biomarkers and therapeutic strategies to target CTCs to prevent or control distant cancer spread. This study provides the first detailed genomic confirmation of the close relation between CTCs and tumor metastases, and illustrates how CTCs can be utilized as a novel approach and rational source for identification of pro-metastatic genes in cancer research. Three individual patient cohorts were utilized in the study. CNV and LOH loci were evaluated initially in metastatic melanoma patients (n=13) in a discovery cohort. SNP loci that harbored CNV/LOH in CTCs were then separately verified for: (a) presence in distant organ metastasis (AJCC Stage IV melanoma) (n=27), and (b) relevance to prognosis in regional melanoma metastasis (AJCC Stage III melanoma) (n=35). The first discovery patient cohort group was utilized for capture of CTCs, and consisted of peripheral blood mononuclear cell (PBMC) and tumor specimens from metastatic melanoma patients (n=13). CTC-related loci were verified in a second cohort of patients with Stage IV distant organ metastases (n=27), including 15 brain, 4 lung, and 8 gastrointestinal (bowel, liver) metastases. The third patient cohort consisted of early passage (<12) established melanoma cell lines derived from 35 regional melanoma metastases (Stage III) for evaluation of the prognostic utility of the CTC-associated aberrant loci.
2014-07-01 | E-GEOD-43934 | biostudies-arrayexpress
Project description:In this comprehensive study, the authors have developed concise models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 Immune Checkpoint Blockade (ICB) treatment in individual tumors. It's important to note that their validation was performed in smaller, independent cohorts, constrained by data availability. The authors have developed two Logistic Regression based models for Ipilimumab treated and Ipilimumab naive patients with metastatic melanoma. The main predictive features for the Ipilimumab treated patients are MHC-II HLA, LDH at treatment initiation and the presence of lymph node metastases (LN met), chosen using forward selection methodology. The main predictive features for the Ipilimumab naive patients are tumor heterogeneity, tumor ploidy and tumor purity, chosen using forward selection methodology.
Please note that in these models, the output ‘1’ means progressive disease (PD) and ‘0’ means non-PD. The original GitHub repository can be accessed at https://github.com/vanallenlab/schadendorf-pd1
2023-11-17 | MODEL2310150001 | BioModels
Project description:Immunotherapy and targeted therapy dramatically changed the treatment of metastatic melanoma. Yet, many patients do not respond to these treatments and improve the understanding of response and resistance is an urgent need. Thus, we utilized mass spectrometry-based proteomic analysis of 185 metastatic melanoma samples. Metastases from different sites demonstrate differences in cellular processes such as immune, metabolism, translation and proliferation. Complementary epidemiology analysis uncovers prognosis variance between different metastases locations after treated with anti-PD1. Examination of lung melanoma metastases reveals clinical and molecular heterogeneity that mainly reflected in immune-related processes. Analysis of BRAF mutation status and prior treatments with MAPK inhibitors also indicate differences in immune and metabolic processes and suggest a molecular basis for the combination of immunotherapy and targeted therapy. These results shed new light into biology and therapeutic resistant mechanisms and the pathogenesis of metastatic melanoma.
2020-12-23 | PXD020618 | Pride
Project description:The phenomenon that metastatic lesion developed on injured sites has long been recognized in a number of cancers, such as melanoma. The factors associated with wound healing that attract circulating tumor cells have remained unknown, however. A patient with acral lentiginous melanoma presented with a metastatic lesion that appeared 1 month after trauma. To explore the molecular mechanism underlying the promotion of wound metastasis in melanoma, we performed microarray analysis of the metastatic lesions (n = 2) and the primary lesions (n = 3) of the patient. Using Human Genome U133 Plus 2.0 array, we compared global gene expression profiles of tissues derived from the patient’s primary (n = 3) and wound metastatic (n = 2) lesions to search for particular biological functions in genes of which expression intensities were increased in the wound metastasic lesions of melanoma.
2015-06-26 | E-GEOD-62837 | biostudies-arrayexpress