Whole exome germline sequencing in early-onset prostate cancer patients: Genomic findings and clinical outcomes

Abstract

Background: Whole exome sequencing (WES) furthered our understanding of various tumors. We assessed the occurrence of germline likely pathogenic/pathogenic (LP/P) variants, disease features, and clinical outcomes in early-onset prostate cancer. Methods: This retrospective study (N = 134) included consecutive prostate cancer patients who donated blood samples for research purposes to the Kahn-Sagol-Maccabi biobank. Patients diagnosed at >65 years were excluded. Clinical characteristics were extracted from the medical records. Germline WES was performed with analysis reporting on oncogenetic, two immunogenic, and a secondary minimum list panels (121, 468, 76, and 59 genes, respectively). Results: Median age at diagnosis was 61 (range 46–65) years; 131 (98%) were diagnosed with local disease. The median follow-up time from diagnosis was 14 (range <1–25) years. Of the patients with local disease, 32 (24%) and 10 (8%) had biochemical and distant recurrences, respectively. Twenty-five patients (19%) had ≥1 additional cancer (excluding non-melanoma skin cancer), most frequently bladder (6), colorectal (5), and lymphoma (5). Seven (5%) deaths were reported, with only one related to prostate cancer. LP/P variants were identified in 8 patients (6%), all in genes from the oncogenetic panel: ATM, BRCA1 (in two patients), BRCA2 (in two patients), HOXB13, MUTYH, and MYH7. Of these eight patients, with a median follow-up of 7 years (range <1–15), two (25%) had biochemical recurrences, one had (12.5%) distant recurrence, and no deaths were reported. Conclusions: In this cohort of 134 early-onset prostate cancer patients, we identified germline LP/P variants in an oncogenetic panel in 6% of participants, with no unique clinical outcome.