Landscape of Cyclin Pathway Genomic Alterations Across 5,356 Prostate Cancers: Implications for Targeted Therapeutics.
Oncologist
; 26(4): e715-e718, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33522043
ABSTRACT
The cyclin pathway may confer resistance to standard treatments but also offer novel therapeutic opportunities in prostate cancer. Herein, we analyzed prostate cancer samples (majority metastatic) using comprehensive genomic profiling performed by next-generation sequencing (315 genes, >500× coverage) for alterations in activating and sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), androgen receptor (AR) gene, and coalterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1). Overall, cyclin sensitizing pathway genomic abnormalities were found in 9.7% of the 5,356 tumors. Frequent alterations included CCND1 amplification (4.2%) and CDKN2A and B loss (2.4% each). Alterations in possible resistance genes, RB1 and CCNE1, were detected in 9.7% (up to 54.6% in neuroendocrine) and 1.2% of cases, respectively, whereas AR alterations were seen in 20.9% of tumors (~27.3% in anaplastic). Cyclin sensitizing alterations were also more frequently associated with concomitant AR alterations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Genômica
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article