Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer.

ABSTRACT: We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3C

SUBMITTER: Bova GS 

PROVIDER: S-EPMC4853517 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature