Unknown,Transcriptomics,Genomics,Proteomics

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CaArray_kuppe-00390: Broad: Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome

ABSTRACT: Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. kuppe-00390 Assay Type: Gene Expression Provider: Affymetrix Array Designs: U133AAofAv2 Organism: Homo sapiens (ncbitax) Tissue Sites: Skin Material Types: total RNA, synthetic_RNA, organism_part, whole_organism Disease States: Cutaneous T-cell lymphoma

ORGANISM(S): Homo sapiens

SUBMITTER: Mervi Heiskanen

PROVIDER: E-GEOD-70328 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome.

Shin Jessica J Monti Stefano S Aires Daniel J DJ Duvic Madeleine M Golub Todd T Jones David A DA Kupper Thomas S TS

Blood 20070716 8

Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from ...[more]

PMID: 17638852

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Project description:A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data from four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction, and microarray analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples, the cell lines, and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered together regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study. dobbi-00100 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A Organism: Homo sapiens (ncbitax) Tissue Sites: Kidney, Lung, Stomach, Uterus, Liver, Lymphoid tissue, Ovary, Skin, Adrenal Gland, Lymph_Node Material Types: cell, nuclear_RNA, synthetic_RNA, organism_part, total_RNA Disease States: Recurrent Renal Cell Carcinoma, Squamous Cell Carcinoma,Conventional_Clear_Cell_Renal_Cell_Carcinoma,Gastrointestinal_Stromal_Tumor, Lung_Adenocarcinoma, Leiomyoma, Non neoplastic liver with cirrosis, Stomach Adenocarcinoma, Large Cell Lymphoma, Ovarian Adenocarcinoma, Melanoma, Malignant G1 Stromal Tumor, Adrenal Cortical Adenoma, Metastatic Renal Cell Carcinoma, Malignant Melanoma

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Dataset Information

CaArray_kuppe-00390: Broad: Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome

Publications

Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome.

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