التفاصيل البيبلوغرافية
| العنوان: |
Contrasting genomic profiles from metastatic sites, primary tumors, and liquid biopsies of advanced prostate cancer. |
| المؤلفون: |
Necchi, Andrea, Cucchiara, Vito, Grivas, Petros, Bratslavsky, Gennady, Jacob, Joseph, Spiess, Philippe E., Sokol, Ethan S., Killian, Jonathan Keith, Lin, Douglas, Ramkissoon, Shakti, Huang, Richard S. P., Madison, Russell W., Venstrom, Jeffrey M., Schrock, Alexa B., Danziger, Natalie, Decker, Brennan, Gjoerup, Ole, Graf, Ryon P., Oxnard, Geoffrey R., Tukachinsky, Hanna |
| المصدر: |
Cancer (0008543X); Dec2021, Vol. 127 Issue 24, p4557-4564, 8p |
| مصطلحات موضوعية: |
CIRCULATING tumor DNA, PROSTATE cancer, PROSTATE biopsy, PROSTATE tumors, TUMORS, PROSTATE cancer patients |
| مستخلص: |
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. Tumor tissue genomic alterations from primary prostate tumors and metastatic sites show significant heterogeneity, and this suggests possible tumor evolution, natural selection, and/or tumor adaptation. Circulating tumor DNA testing can be a noninvasive, potentially serial assay that may provide a real‐time representation of the evolutionary cancer state throughout therapy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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