Molecular Profiling to Determine Clonality of Serial Magnetic Resonance Imaging/Ultrasound Fusion Biopsies from Men on Active Surveillance for Low-Risk Prostate Cancer

Palapattu, Ganesh S.; Salami, Simpa S.; Cani, Andi K.; Hovelson, Daniel H.; Vega, Lorena Lazo de la; VanDenBerg, Kelly R.; Bratley, Jarred V.; Liu, Chia Jen; Kunju, Lakshmi P.; Montgomery, Jeff D.; Morgan, Todd M.; Natarajan, Shyam; Huang, Jiaoti; Tomlins, Scott A.; Marks, Leonard S.

doi:10.1158/1078-0432.ccr-16-1454

Cited by 23 publications

(17 citation statements)

References 38 publications

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“…RNA and DNA NGS and bioinformatics methods. RNA and DNA isolation and NGS were performed as detailed in the Supplemental Methods and as previously described (18,38,39). Detailed bioinformatics methods, fusion isoform-and partner-level analyses, AR and AR splice variant analysis, and DNA variant calls and copy number analyses are as previously reported and described in the Supplemental Methods (18,38,40).…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic heterogeneity in multifocal prostate cancer

et al. 2018

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BACKGROUND. Commercial gene expression assays are guiding clinical decision making in patients with prostate cancer, particularly when considering active surveillance. Given heterogeneity and multifocality of primary prostate cancer, such assays should ideally be robust to the coexistence of unsampled higher grade disease elsewhere in the prostate in order to have clinical utility. Herein, we comprehensively evaluated transcriptomic profiles of primary multifocal prostate cancer to assess robustness to clinically relevant multifocality. METHODS. We designed a comprehensive, multiplexed targeted RNA-sequencing assay capable of assessing multiple transcriptional classes and deriving commercially available prognostic signatures, including the Myriad Prolaris Cell Cycle Progression score, the Oncotype DX Genomic Prostate Score, and the GenomeDX Decipher Genomic Classifier. We applied this assay to a retrospective, multi-institutional cohort of 156 prostate cancer samples. Derived commercial biomarker scores for 120 informative primary prostate cancer samples from 44 cases were determined and compared. RESULTS. Derived expression scores were positively correlated with tumor grade (r S = 0.53-0.73; all P < 0.001), both within the same case and across the entire cohort. In cases of extreme gradediscordant multifocality (co-occurrence of grade group 1 [GG1] and ≥GG4 foci], gene expression scores were significantly lower in low-(GG1) versus high-grade (≥GG4) foci (all P < 0.001). No significant differences in expression scores, however, were observed between GG1 foci from prostates with and without coexisting higher grade cancer (all P > 0.05). CONCLUSIONS. Multifocal, low-grade and high-grade prostate cancer foci exhibit distinct prognostic expression signatures. These findings demonstrate that prognostic RNA expression assays performed on low-grade prostate cancer biopsy tissue may not provide meaningful information on the presence of coexisting unsampled aggressive disease.

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Section: Methodsmentioning

confidence: 99%

Transcriptomic heterogeneity in multifocal prostate cancer

et al. 2018

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“…Transcriptomic analysis also identified genes associated with tumour aggression in mpMRI-visible tumours, such as noncoding RNA SCHLAP1 (linked to prostate cancer progression), several small nuclear RNAs [2] , and angiogenesis factor VEGF [46] . Indeed, mutations in tumorigenic drivers such as SPOP and IDH1 have been found even in lower-grade mpMRI-visible tumours [47] .…”

Section: Evidence Synthesismentioning

confidence: 99%

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Norris

Simpson

Parry

et al. 2020

European Urology Open Science

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Context Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue ( PTEN ) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.

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“…In the present study, biopsy follow-up, also MRI-guided, was mandated in the protocol and completed in 28/29 patients. Tracking of biopsy sites, a function of fusion devices, enables re-sampling of previous cancer foci, within or without of MRI-visible lesions 21,26 , and was used routinely to increase sensitivity of follow-up biopsy. Few prior studies of cryoablation have employed a protocol mandating a follow-up biopsy, and according to a recent literature review 25 , none by MRI-guided biopsy before and after treatment.…”

Section: Commentmentioning

confidence: 99%