MP90-06 FULL EXOME SEQUENCING, COPY NUMBER VARIATION AND TRANSCRIPTOME ANALYSES REVEALS DIVERSITY AND MUTATIONAL EVOLUTION IN A LONGITUDINAL SERIES OF SURGICAL PROSTATE CANCER BONE METASTASES FROM A PATIENT WITH PROGRESSIVELY THERAPY-RESISTANT CANCER.

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP90-06 FULL EXOME SEQUENCING, COPY NUMBER VARIATION AND TRANSCRIPTOME ANALYSES REVEALS DIVERSITY AND MUTATIONAL EVOLUTION IN A LONGITUDINAL SERIES OF SURGICAL PROSTATE CANCER BONE METASTASES FROM A PATIENT WITH PROGRESSIVELY THERAPY-RESISTANT CANCER. Christina Jamieson, Michelle Muldong, Michael A. Liss, Seung Chol Park, Theresa Mendoza, Abigail Gallegos, Lee Edsall, Unwanaobong Nseyo, Olga Miakicheva, Brittany Burton, Danielle Burner, Amy Strasner, Christopher J. Kane, Anna A. Kulidjian, and Theresa Gaasterland Christina JamiesonChristina Jamieson More articles by this author , Michelle MuldongMichelle Muldong More articles by this author , Michael A. LissMichael A. Liss More articles by this author , Seung Chol ParkSeung Chol Park More articles by this author , Theresa MendozaTheresa Mendoza More articles by this author , Abigail GallegosAbigail Gallegos More articles by this author , Lee EdsallLee Edsall More articles by this author , Unwanaobong NseyoUnwanaobong Nseyo More articles by this author , Olga MiakichevaOlga Miakicheva More articles by this author , Brittany BurtonBrittany Burton More articles by this author , Danielle BurnerDanielle Burner More articles by this author , Amy StrasnerAmy Strasner More articles by this author , Christopher J. KaneChristopher J. Kane More articles by this author , Anna A. KulidjianAnna A. Kulidjian More articles by this author , and Theresa GaasterlandTheresa Gaasterland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2550AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer metastasizes to bone in 50-90% of patients with advanced disease yet relatively little is known about genome-wide genetic alterations in prostate cancer bone metastases. Recent whole genome, exome and transcriptome sequencing studies on prostate cancer have identified recurrent mutations and gene rearrangements such as the TMPRSS2-ERG fusion and variants of the androgen receptor (AR). Here we determined bone metastatic prostate cancer genomic and transcriptomic variation in a longitudinal series of surgical bone metastasis samples from the same patient. METHODS We collected surgical prostate cancer bone metastases samples at the time of orthopaedic repair surgery with matched peripheral blood and prostatectomy tissue and established a new bone-niche xenograft model with a primary patient surgical prostate cancer bone metastasis, PCSD1 (Prostate Cancer San Diego 1). Next generation whole exome sequencing was performed on genomic DNA extracted from flash frozen samples or single cell suspensions of surgical bone metastasis specimens, peripheral blood mononuclear cells and from primary FFPE archived prostatectomy tissue. DNA libraries were prepared using the NimbleGen DNA Sample Preparation kit and sequencing was performed on the Illumina HiSeq 2000 sequencing 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 GeneChip 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. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1146-e1147 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Christina Jamieson More articles by this author Michelle Muldong More articles by this author Michael A. Liss More articles by this author Seung Chol Park More articles by this author Theresa Mendoza More articles by this author Abigail Gallegos More articles by this author Lee Edsall More articles by this author Unwanaobong Nseyo More articles by this author Olga Miakicheva More articles by this author Brittany Burton More articles by this author Danielle Burner More articles by this author Amy Strasner More articles by this author Christopher J. Kane More articles by this author Anna A. Kulidjian More articles by this author Theresa Gaasterland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...