Contrasting genomic profiles from metastatic sites, primary tumors, and liquid biopsies of advanced prostate cancer.
Cancer
; 127(24): 4557-4564, 2021 12 15.
Article
em En
| MEDLINE
| ID: mdl-34379803
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. TMPRSS2ERG 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
DNA Tumoral Circulante
Limite:
Humans
/
Male
Idioma:
En
Revista:
Cancer
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália