Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Amplification and overexpression of vinculin are associated with increased tumor cell proliferation and progression in advanced prostate cancer

ABSTRACT: We analyzed the 10q22 amplification in advanced prostate cancer and subjected the genes located in the common amplified region to an RNAi screen. We found vinculin as the most promising candidate gene and analyzed its protein expression on more than 400 prostate cancers by using the tissue micrarray (TMA) technology. We discovered a strong correlation between amplification of the vinculin gene and increased protein expression. Further, vinculin protein expression was strongly associated with increased tumor cell proliferation. We isolated DNA from four 10q22 amplified cell lines (PC-3, MFM-223, SK-BR-3, ME-180). Genomic DNA was digested with the restriction enzymes RSA I / ALU I and then labeled with Cy5 using a Klenow-based commercial kit (Invitrogen). Each sample was hybridized with a pooled normal (46,XX) reference (Promega) to Agilent 244k CGH arrays. This experiment allowed us to define the common amplified region of the 10q22 amplification.

ORGANISM(S): Homo sapiens

SUBMITTER: Christian Ruiz

PROVIDER: E-GEOD-24216 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer.

Ruiz Christian C Holz David R DR Oeggerli Martin M Schneider Sandra S Gonzales Irma M IM Kiefer Jeffrey M JM Zellweger Tobias T Bachmann Alexander A Koivisto Pasi A PA Helin Heikki J HJ Mousses Spyro S Barrett Michael T MT Azorsa David O DO Bubendorf Lukas L

The Journal of pathology 20110105 4

Androgen withdrawal is the standard treatment for advanced prostate cancer. Although this therapy is initially effective, nearly all prostate cancers become refractory to it. Approximately 15% of these castration-resistant prostate cancers harbour a genomic amplification at 10q22. The aim of this study was to explore the structure of the 10q22 amplicon and to determine the major driving genes. Application of high-resolution array-CGH using the 244k Agilent microarrays to cell lines with 10q22 am ...[more]

PMID: 21294127

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Project description:Genomic analysis of many cancers has led to the identification of novel targets and the development of personalized, targeted therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. Clinical specimens typically contain variable degrees of non-tumor cells that can mask a potentially critical genomic signature, leaving important clinically relevant events undetected. When analysis is limited to a smaller number of specimens, the effects of heterogeneity within each sample is magnified. In light of these challenges, we used DNA content based flow cytometry to isolate clonal tumor populations from a series of rare cancers for genomic analysis: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. These purified clonal populations are then subject to high definition measurement of copy number aberrations by objectively measuring the height and boundaries of amplicons and by discriminating homozygous from partial deletions. Ranking of these events by copy number facilitates the identification of highly selected aberrations. This approach can garner useful information from a single biopsy. In the cases we describe, several potential therapeutic targets were identified and genomic aberrations correlated with the phenotypic behavior. We propose that clonal genomic analysis can generate unique hypotheses and guide the development of clinical advances for these and other rare tumors. We applied DNA content based flow sorting to isolate the nuclei of clonal populations from tumor biopsies. We coupled this strategy with oligonucleotide array CGH (aCGH) thereby obtaining high definition genomic profiles of clonal populations from different rare tumors including pancreatic neuroendocrine cancers, adrenal leiomyosarcoma, anal carcinoma, and cholangiocarcinoma.

Dataset Information

Amplification and overexpression of vinculin are associated with increased tumor cell proliferation and progression in advanced prostate cancer

Publications

Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer.

Similar Datasets

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