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CancerMap project prostate cancer microarray dataset

ABSTRACT: Microarray expression profiling has currently failed to provide a consistent classification for human prostate cancer. Such classifications are important because they provide a framework for the identification of new biomarkers of clinical behavior and for the development of targeted therapies. We hypothesize that previous studies have been unsuccessful because of their failure to take into account the well documented occurrence of prostate cancer multifocality and genetic heterogeneity. We have invented a novel method for collecting whole RNALater preserved ‘research slices’ from prostatectomy specimens that, for the first time, allows the mapping of multifocality and of genetic heterogeneity in prostate cancer to be integrated with the selection of samples for expression microarray analysis. For each specimen we will construct a map of the regions of cancer and of their ERG gene rearrangement status from whole mount formalin fixed sections immediately juxtaposed to the ‘research slice’. Only foci of cancers containing a homogeneous pattern of ERG gene alteration will be selected for study. A pilot study has already demonstrated the feasibility of this approach, and provides initial evidence that cancers may be stratified into at least two prognostically distinct categories. Novel biomarkers defining distinct prostate cancer categories will be verified and validated in future studies linked to clinical trials.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE94767 | GEO | 2017/03/13

SECONDARY ACCESSION(S): PRJNA373993

REPOSITORIES: GEO

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Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen Test Cohort: 388 cases from the population based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Validation cohort: The PhysiciansM-bM-^@M-^Y Health Study (PHS) cohort included 116 US men diagnosed with incidental prostate cancer between 1983 and 2003; 455 cases were annotated for TMPRSS2-ERG fusion. Test Set: GSM208029 ... GSM208392 Validation Set: GSM208404 ... GSM208512

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CancerMap project prostate cancer microarray dataset

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