Evaluating Germline Testing Panels in Southern African Males With Advanced Prostate Cancer

• DOI: 10.6004/jnccn.2022.7097
• Publication Date: 2023-03-10T20:34:21Z
• Authors: Kazzem Gheybi; Jue Jiang; Shingai B.A. Muta...; Pamela X.Y. Soh; Zsofia Kote-Jarai; Weerachai Jaratle...; Rosalind A. Eeles; M.S. Riana Bornman; Vanessa M. Hayes
• Keywords: CHEK2; PALB2

Germline testing for prostate cancer is on the increase, with clinical implications risk assessment, treatment, and management. Regardless of family history, NCCN recommends germline patients metastatic, regional, very-high-risk localized, high-risk localized cancer. Although African ancestry a significant factor aggressive cancer, due to lack available data no criteria have been established ethnic minorities.Through deep sequencing, we interrogated 20 most common panel genes in 113 Black South males presenting largely advanced Bioinformatic tools were then used identify pathogenicity variants.After identified 39 predicted deleterious variants (16 genes), further computational annotation classified 17 as potentially oncogenic (12 genes; 17.7% patients). Rare pathogenic included CHEK2 Arg95Ter, BRCA2 Trp31Arg, ATM Arg3047Ter (2 patients), TP53 Arg282Trp. Notable unknown novel Leu3038Ile patient early-onset disease, whereas FANCA Arg504Cys RAD51C Arg260Gln reported history Overall, rare or familial-associated 6.9% (5/72) 9.2% (8/87) Gleason score ≥8 ≥4 + 3 respectively.In this first-of-its-kind study southern males, provide support inclusion advanced, early-onset, familial genetic testing, indicating value 30% current gene panels. Recognizing limitations highlights an urgent need establish guidelines men ancestry. We rationale considering lowering pathologic diagnostic call genome-wide interrogation ensure best possible African-relevant panel.