biostudies-literatureLiss MANational Cancer Institute (NCI)National Human Genome Research Institute (NHGRI)U.S. Department of Defense (DOD)U.S. Department of DefenseNational Cancer InstituteNHGRI NIH HHSNCI NIH HHSNational Human Genome Research Institute1500-1511https://www.ebi.ac.uk/biostudies/studies/S-EPMC11528207biostudies-literatureUnknown33(11)<h4>Background</h4>Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic, and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.<h4>Methods</h4>We established a prospective, multi-institutional cohort of men with grade group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantifyCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive OncologyUpgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.PMC11528207R01 CA270108T32 HG002536P30CA016042F31 CA281168U01 CA086402U01CA113913U01 CA214194T32HG002536U01CA214194P50CA211024R01CA270108U2CCA271894W81XWH-22-1-0247U01CA086402P30 CA016042U24 CA086368U24CA086368W81XWH-15-1-0441U01 CA113913P50 CA211024U2C CA271894Thompson IMTroyer DALiu MLin DWEng SEKhani FLiss MALopez CKagan JKlein EAZheng YBrooks JDTian MZeltser NPatel YYamaguchi TNSemmes OJMosquera JMTewari AKBoutros PCWei JTRobinson BDLeach RJSanda MGAasad MfalseUpgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.<h4>Background</h4>Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic, and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.<h4>Methods</h4>We established a prospective, multi-institutional cohort of men with grade group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify2024-01-01T00:00:00Z2024 Nov2026-07-09T10:58:12.126Z2025-04-04T00:26:32.721ZS-EPMC115282073915840410.1158/1055-9965.EPI-24-032610.1158/1055-9965.epi-24-0326