Genomic and epigenomic evolution of metastatic prostate cancer: the first warm autopsy in China

Abstract

AbstractBackgroundThe development and expansion of warm autopsy program have important implications in dissecting the heterogeneity during cancer dissemination and resistance. However, in China, the practice of warm autopsy has not yet been officially launched and documented.MethodsTo explore and establish the procedures and standards for warm autopsy in China, we followed the disease course of a male patient with terminal metastatic prostate cancer. We assembled a multidisciplinary team to perform warm autopsy immediately after death. Through longitudinal sampling from biopsy and autopsy, we performed integrative and comprehensive genomic and epigenomic analysis using multi-omics approaches.ResultsWe traced the dynamic evolution and heterogeneity of this prostate tumor, and identified many critical driver events in both the original tumor and its disseminations. TruncatedCDKN1Bmay result in downregulation of expression, which represent a key driver event in the metastatic progression of prostate cancer. We also delineated the congruence of genetic and epigenetic clonal evolution during tumor metastasis.ConclusionsOur data and analysis elucidated the mechanisms and drivers during metastasis, which represent a valuable resource for the study and treatment of prostate cancer. We also call on more investigators to improve warm autopsy of prostate cancer for clinical and experimental investigations.