title: Molecular Profiling to Determine Clonality of Serial Magnetic Resonance Imaging/Ultrasound Fusion Biopsies from Men on Active Surveillance for Low-Risk Prostate Cancer.
abstract: Purpose:To determine whether MRI/ultrasound (MRI/US) fusion biopsy facilitates longitudinal resampling of the same clonal focus of prostate cancer and to determine whether high-grade cancers can evolve from low-grade clones.Experimental Design:All men on active surveillance who underwent tracking MRI/US fusion biopsy of Gleason 6 prostate cancer, on at least two distinct occasions, between 2012 and 2014 were enrolled. MRI/US fusion was used to track and resample specific cancer foci. IHC for ERG and targeted RNA/DNA next-generation sequencing (NGS) were performed on formalin-fixed paraffin-embedded prostate biopsy specimens to assess clonality.Results:Thirty-one men with median age and PSA of 65 years and 4.6 ng/mL, respectively, were analyzed. The median sampling interval was 12 months (range, 5-35). Of the 26 evaluable men, ERG IHC concordance was found between initial and repeat biopsies in 25 (96%), indicating resampling of the same clonal focus over time. Targeted NGS supported ERG IHC results and identified unique and shared driving mutations, such asIDH1andSPOP, in paired specimens. Of the nine men (34.6%) who were found to have Gleason ≥7 on repeat biopsy, all displayed temporal ERG concordance. Prioritized genetic alterations were detected in 50% (13/26) of paired samples. Oncogenic mutations were detected in 22% (2/9) of Gleason 6 cancers prior to progression and 44% (4/9) of Gleason ≥7 cancers when progression occurred.Conclusions:Precise tracking of prostate cancer foci via MRI/US fusion biopsy allowed subsequent resampling of the same clonal focus of cancer over time. Further research is needed to clarify the grade progression potential of Gleason 6 prostate cancer.Clin Cancer Res; 23(4); 985-91. ©2016 AACR.
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan. gpalapat@med.umich.edu tomlinss@med.umich.edu LMarks@mednet.ucla.edu.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Simpa S
authors.initials: SS
authors.lastname: Salami
authors.affiliation: Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Andi K
authors.initials: AK
authors.lastname: Cani
authors.affiliation: Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Hovelson
authors.affiliation: Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Lorena
authors.initials: L
authors.lastname: Lazo de la Vega
authors.affiliation: Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Vandenberg
authors.affiliation: Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jarred V
authors.initials: JV
authors.lastname: Bratley
authors.affiliation: Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Montgomery
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Morgan
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Shyam
authors.initials: S
authors.lastname: Natarajan
authors.affiliation: Department of Pathology, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan. gpalapat@med.umich.edu tomlinss@med.umich.edu LMarks@mednet.ucla.edu.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.|Department of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California. gpalapat@med.umich.edu tomlinss@med.umich.edu LMarks@mednet.ucla.edu.
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Marks
mesh_terms: D000368:Aged; D001706:Biopsy; D060965:Clonal Evolution / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D014463:Ultrasonography / Q000379:methods
chemical_list: D009363:Neoplasm Proteins