MP90-07 THE PHENOMENON OF EPITHELIAL-MESENCHYMAL TRANSITION IS ASSOCIATED WITH THE PROGRESSION OF PROSTATE CANCER

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platform.Affymetrix Oncoscan analysis was used to determine genome-wide copy number and loss-of-heterozygosity (LOH) profiles.Whole transcriptome analysis was performed using Affymetrix Gen-eChip Human Transcriptome Array 2.0.RESULTS: We generated full exome sequences to determine the impact of acquired somatic mutations driving lethal and recurrent bone metastatic CRPC, as well as impact of treatment first with androgen deprivation therapy (ADT), then additional radiation plus docetaxel and, lastly, abiraterone plus cabazitaxel from sequential surgeries in a single patient.We also sequenced the whole exome of PCSD1 intra-femoral xenograft tumors to determine the impact of in vivo xenograft models on the exomic integrity of prostate cancer bone metastasis.Sequence analysis has identified SNVs, small insertion and deletions, translocations and additional gene rearrangements that are shared as well as unique to each bone metastatic sample.Integration of exome sequencing, CNV and microarrays revealed activation of WNT5a in prostate cancer bone metastases.CONCLUSIONS: This is a whole exome and transcriptome report on a unique set of samples from one patient: blood (germ line), primary tumor, surgical bone metastasis sample #1 after ADT, bone metastasis #2 after ADT, radiation and docetaxel, bone metastasis #3 after abiraterone, radiation, plus cabazitaxel.Analysis of surgical prostate cancer bone metastases at different stages of treatment and progression in this patient provides a foundation to profile genomic diversity in recurrent bone metastatic prostate cancer.Mutations and activation of Wnt5a are being tested int the matched patient derived xenograft, PCSD1.

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