Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression profile of primary and wound metastatic lesions of melanoma

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Keitaro Fukuda

PROVIDER: E-GEOD-62837 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.

Fukuda Keitaro K Sugihara Eiji E Ohta Shoichiro S Izuhara Kenji K Funakoshi Takeru T Amagai Masayuki M Saya Hideyuki H

PloS one 20150617 6

Tissue injury promotes metastasis of several human cancers, although factors associated with wound healing that attract circulating tumor cells have remained unknown. Here, we examined the primary and metastatic lesions that appeared 1 month after trauma in a patient with acral lentiginous melanoma. The levels of mRNA for periostin (POSTN), type 1 collagen, and fibronectin were significantly increased in the metastatic lesion relative to the primary lesion. The increase of these extracellular ma ...[more]

PMID: 26083413

Similar Datasets

Project description:An evaluation of multifocal lesions from patients with in-transit extremity melanoma to determine if all lesions from a patient harbor homogeneous patterns of gene expression; Gene expression profiling studies can help guide treatment for cancer patients by providing tools in the form of gene-expression signatures to characterize a tumor in terms of underlying biology, predicted response to therapy, metastatic progression and/or recurrence. The utility of gene signatures for defining therapeutic strategies in the treatment of extremity in-transit melanoma will be dependent on the genetic relationship between the multifocal lesions typically present in this disease and the extent to which a single lesion is representative of residual tumor burden. Using microarray-based gene expression profiling we examined 43 in-transit melanoma lesions across 17 patients with multifocal disease to determine whether one lesion could accurately characterize the underlying biology and genetic profile of a patient's tumor. Principal component analysis, unsupervised hierarchical clustering, one-way analysis of variance (ANOVA) and gene signatures predictive of chemosensitivity and oncogenic pathway activation showed gene expression patterns to be highly similar (p-values: <0.006; average r = 0.979) between lesions from a single patient but to be significantly different across patients (p<0.05). These findings demonstrate that individual melanoma tumor nodules in patients with multifocal disease are genetically similar and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the utilization of gene expression profiling in clinical trials of targeted therapy in melanoma allowing for more rational identification of candidates for specific therapies. Experiment Overall Design: Gene expression profiles were obtained from 43 lesions across 17 patients and evaluated using several different algorithms to determine the degree of correlation across multifocal lesions and to evaluate patterns of gene expression that are different across patients

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).

Dataset Information

Expression profile of primary and wound metastatic lesions of melanoma

Publications

Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure