Men with early-onset prostate cancer are at increased risk for cancer-related mortality, yet the prevalence and spectrum of molecular alterations in this patient population is unknown. Here, we analyze comprehensive genomic profiling data to characterize the molecular drivers of early-onset prostate cancer in patients with clinically advanced and metastatic disease.
Next-generation sequencing was ordered as a part of routine clinical care for 10,189 patients with prostate cancer between 02/2013 and 03/2020 using commercially available comprehensive genomic profiling.
Deidentified genomic data for 10,189 unique patients with prostate cancer were obtained (median age = 66 y, range = 34-90 y). 439 patients were ≤50 y (4.3%), 1928 patients were between ages of 51 and 59 y (18.9%), and 7822 patients were ≥60 y (76.8%). Of metastatic biopsy sites, lymph node, liver, and bone were the most common in all groups, accounting for 60.2% of all specimens. Overall, 97.4% of patients harbored pathologic genomic alterations. The most commonly altered genes were TP53, TMPRSS2-ERG, PTEN, AR, MYC, MLL2, RAD21, BRCA2, APC, SPOP, PIK3CA, RB1, MLL3, CDK12, ATM, and CTNNB1. Patients ≤50 y harbored significantly more TMPRSS2-ERG fusions than patients ≥60 y, while AR copy number alterations as well as SPOP and ASXL1 mutations were significantly less frequent.
Clinically advanced and metastatic early-onset prostate cancer is a distinct clinical subgroup with characteristic genomic alterations including increased frequency of TMPRSS2-ERG fusions and fewer AR, SPOP, and ASXL1 alterations.
Prostate cancer and prostatic diseases. 2021 Jan 08 [Epub ahead of print]
Zachary R Chalmers, Michael C Burns, Ericka M Ebot, Garrett M Frampton, Jeffrey S Ross, Maha H A Hussain, Sarki A Abdulkadir
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Foundation Medicine, Inc, Cambridge, MA, USA., Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ., Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/33420417