標題: Multiregional Radiogenomic Assessment of Prostate Microenvironments with Multiparametric MR Imaging and DNA Whole-Exome Sequencing of Prostate Glands with Adenocarcinoma
作者: Jamshidi, Neema
Margolis, Daniel J.
Raman, Steven
Huang, Jiaoti
Reiter, Robert E.
Kuo, Michael D.
電機學院
College of Electrical and Computer Engineering
公開日期: 1-Jul-2017
摘要: Purpose: To assess the underlying genomic variation of prostate gland microenvironments of patients with prostate adenocarcinoma in the context of colocalized multiparametric magnetic resonance (MR) imaging and histopathologic assessment of normal and abnormal regions by using whole-exome sequencing. Materials and Methods: Six patients with prostate adenocarcinoma who underwent robotic prostatectomy with whole-mount preservation of the prostate were identified, which enabled spatial mapping between preoperative multiparametric MR imaging and the gland. Four regions of interest were identified within each gland, including regions found to be normal and abnormal via histopathologic analysis. Whole-exome DNA sequencing (. 50 times coverage) was performed on each of these spatially targeted regions. Radiogenomic analysis of imaging and mutation data were performed with hierarchical clustering, phylogenetic analysis, and principal component analysis. Results: Radiogenomic multiparametric MR imaging and whole-exome spatial characterization in six patients with prostate adenocarcinoma (three patients, Gleason score of 3 + 4; and three patients, Gleason score of 4 + 5) was performed across 23 spatially distinct regions. Hierarchical clustering separated histopathologic analysis-proven high-grade lesions from the normal regions, and this reflected concordance between multiparametric MR imaging and resultant histopathologic analysis in all patients. Seventy-seven mutations involving 29 cancer-associated genes across the 23 spatially distinct prostate samples were identified. There was no significant difference in mutation load in cancer-associated genes between regions that were proven to be normal via histopathologic analysis (34 mutations per sample +/- 19), mildly suspicious via multiparametric MR imaging (37 mutations per sample +/- 21), intermediately suspicious via multiparametric MR imaging (31 mutations per sample +/- 15), and high-grade cancer (33 mutations per sample +/- 18) (P =.30). Principal component analysis resolved samples from different patients and further classified samples (regardless of histopathologic status) from prostate glands with Gleason score 3 + 4 versus 4 + 5 samples. Conclusion: Multiregion spatial multiparametric MR imaging and whole-exome radiogenomic analysis of prostate glands with adenocarcinoma shows a continuum of mutations across regions that were found via histologic analysis to be high grade and normal. (C) RSNA, 2017
URI: http://dx.doi.org/10.1148/radiol.2017162827
http://hdl.handle.net/11536/145653
ISSN: 0033-8419
DOI: 10.1148/radiol.2017162827
期刊: RADIOLOGY
Volume: 284
起始頁: 109
結束頁: 119
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