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Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

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[Technical Report, Final Report]

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Johns Hopkins University

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Prostate cancer PCA is a clinically and genetically heterogeneous and the development of a molecular classification is critical to distinguish lethal from indolent tumors and minimize overtreatment. Genomic alterations of the PTEN and ERG genes are among the most common in PCA and there is an interest in exploiting these alterations for routine risk assessment. We found that PTEN loss is most strongly associated with PCA death in patients whose tumors do not carry an ERG gene rearrangement, suggesting that ERG absence strengthens PTEN loss association with lethal progression. Despite the widely accessible PTENERG molecular classification, our understanding of their biological interaction along PCA progression remains very limited. Hence, in our study we will perform a comprehensive molecular profiling of well-annotated PCA samples in relation to PTEN and ERG status. Our goals are threefold 1 to confirm that PTENERG double negative tumors are the most aggressive 2 to characterize the expression profiles associated with PTEN and ERG alterations and 3 to determine whether such expression profiles can be used to improve PCA patient stratification into different risk groups.


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[A, Approved For Public Release]