Post-Biopsy Cell-Free DNA From Blood: An Open Window on Primary Prostate Cancer Genetics and Biology

Frontiers in Oncology

Marinella Corbetta¹  Michele Giunta¹  Massimo Lazzeri¹  Monica Zuradelli²  Giulia Soldà³  Giovanni Lughezzani³  Giorgio Guazzoni³  Alberto Saita³  Paolo Casale³  Stefano Duga³  Chiara Chiereghin³  Rosanna Asselta³  Rodolfo Hurle³  Nicolò Maria Buffi³  Ilaria De Simone³ 

[1] Department of Biomedical Sciences, Humanitas University, Milan, Italy;IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy;IRCCS Humanitas Research Hospital, Milan, Italy;

关键词: circulating cell-free DNA;    circulating tumor DNA;    primary prostate cancer;    biopsy;    biomarker;   

DOI  :  10.3389/fonc.2021.654140

来源: DOAJ

【 摘 要 】

Circulating cell-free DNA (ccfDNA), released from normal and cancerous cells, is a promising biomarker for cancer detection as in neoplastic patients it is enriched in tumor-derived DNA (ctDNA). ctDNA contains cancer-specific mutations and epigenetic modifications, which can have diagnostic/prognostic value. However, in primary tumors, and in particular in localized prostate cancer (PCa), the fraction of ctDNA is very low and conventional strategies to study ccfDNA are unsuccessful. Here we demonstrate that prostate biopsy, by causing multiple injuries to the organ, leads to a significant increase in plasma concentration of ccfDNA (P<0.0024) in primary PCa patients. By calculating the minor allele fraction at patient-specific somatic mutations pre- and post-biopsy, we show that ctDNA is significantly enriched (from 3.9 to 164 fold) after biopsy, representing a transient “molecular window” to access and analyze ctDNA. Moreover, we show that newly released ccfDNA contains a larger fraction of di-, tri- and multi-nucleosome associated DNA fragments. This feature could be exploited to further enrich prostate-derived ccfDNA and to analyze epigenetic markers. Our data represent a proof-of-concept that liquid tumor profiling from peripheral blood performed just after the biopsy procedure can open a “valuable molecular metastatic window” giving access to the tumor genetic asset, thus providing an opportunity for early cancer detection and individual genomic profiling in the view of PCa precision medicine.

【 授权许可】

Unknown