Contrasting genomic profiles from metastatic sites, primary tumors, and liquid biopsies of advanced prostate cancer.

Abstract

BACKGROUND:

This study assessed the contrasting genomic profiles from the primary tumors (PTs), metastatic (MET) sites, and circulating tumor DNA (ctDNA) of patients with prostate cancer (PC).

METHODS:

A total of 1294 PC tissue specimens and 2462 ctDNA specimens underwent hybrid capture-based comprehensive genomic profiling (CGP). Specimens included tissue from PTs; MET biopsies from bone, liver (LIV), lung (LU), brain (BN), lymph node, and soft tissue sites; and ctDNA.

RESULTS:

Differences in alteration frequencies between PT, MET, and ctDNA specimens for selected genes were observed. TMPRSS2:ERG fusion frequencies were similar between PTs and MET sites (35% vs 33%) but varied among MET sites. Genomic alterations (GAs) in AR were lowest in PTs (2%) and highest in MET sites (from 24% in LU to 50% in LIV). BN had the highest genomic alterations/tumor (8) and enrichment for PTEN GAs. The BRCA2 GA frequency varied from 0% in BN to 15% in LIV. ERBB2 amplification was increased in MET sites in comparison with PTs. RB1 GAs were increased in LIV. Biomarkers potentially associated with an anti-PD(L)1 response included CDK12 GAs (16% in LU) and a microsatellite instability-high status (29% in BN). Analyses of ctDNA featured a broad spectrum of GAs similar to those detected across MET sites.

CONCLUSIONS:

CGP of PTs, MET sites, and ctDNA in PC exhibited differences most likely associated with tumor progression, clonal evolution, and exposure to systemic therapies; ctDNA can also capture a broad range of potential therapeutic opportunities for patients with PC.

• Authors: Andrea Necchi, Vito Cucchiara, Petros Grivas, Gennady Bratslavsky, Joseph Jacob, Philippe E Spiess, Ethan S Sokol, Jonathan Keith Killian, Douglas Lin, Shakti Ramkissoon, Richard S P Huang, Russell W Madison, Jeffrey M Venstrom, Alexa B Schrock, Natalie Danziger, Brennan Decker, Ole Gjoerup, Ryon P Graf, Geoffrey R Oxnard, Hanna Tukachinsky, Jeffrey S Ross
• Journal: Cancer (Cancer) Vol. 127 Issue 24 Pg. 4557-4564 (12 15 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 34379803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 American Cancer Society.

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA

Topics

• Biomarkers, Tumor (genetics)
• Circulating Tumor DNA (genetics)
• Genomics
• High-Throughput Nucleotide Sequencing
• Humans
• Liquid Biopsy
• Male
• Microsatellite Instability
• Mutation
• Prostatic Neoplasms (genetics)