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

Background The 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. Methods To 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. Results We traced the dynamic evolution and heterogeneity of this prostate tumor, and identified many critical driver events in both the original tumor and its disseminations. Truncated CDKN1B may 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. Conclusions Our 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Promote Clinical Skills and Innovation Ability of Municipal Hospitals Project (SHDC2020CR6007), Shanghai Rising-Star Program (20QA1411800) and National Natural Science Foundation of China (82022055). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Permission for warm autopsy was obtained before the death, with consent provided by the patient and the family members. After death, consent was obtained by the family members with the witness by the operator and the ethics committee. Written informed consent was obtained in accordance with Chinese legislation. Sample collection and study were approved by the ethical board at Changhai Hospital in China (No: TMEC2014-001, No: CHEC2019-165). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The sequencing data in BAM format are available at the Genome Sequence Archive (GSA) for Human at the BIG Data Center (), Beijing Institute of Genomics with the accession number PRJCA010385.