Open AccessLandscape of Cyclin Pathway Genomic Alterations Across 5,356 Prostate Cancers: Implications for Targeted Therapeutics
Author(s) -
Jardim Denis L.,
Millis Sherri Z.,
Ross Jeffrey S.,
Woo Michelle SueAnn,
Ali Siraj M.,
Kurzrock Razelle
Publication year - 2021
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1002/onco.13694
Subject(s) - cdkn2a , cancer research , medicine , cyclin dependent kinase 6 , prostate cancer , cyclin d1 , cancer , oncology , cell cycle
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.