Jamshidi Neema, Margolis Daniel J, Raman Steven, Huang Jiaoti, Reiter Robert E, Kuo Michael D
From the Departments of Radiological Sciences (N.J., S.R., M.D.K.) and Urology (R.E.R.), University of California, Los Angeles-David Geffen School of Medicine, 10833 LeConte Ave, Box 951721, CHS 17-135, Los Angeles, CA 90095-1721; Department of Radiology, Weill Cornell Imaging, New York-Presbyterian Hospital, New York, NY (D.J.M.); Department of Pathology, Duke University School of Medicine, Durham, NC (J.H.); and College of Electrical and Computer Engineering, National Chiao Tung University, HsinChu, Taiwan (M.D.K.).
Radiology. 2017 Jul;284(1):109-119. doi: 10.1148/radiol.2017162827. Epub 2017 Apr 28.
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. RSNA, 2017 Online supplemental material is available for this article.
目的 通过全外显子组测序，在共定位多参数磁共振（MR）成像以及对正常和异常区域进行组织病理学评估的背景下，评估前列腺腺癌患者前列腺微环境的潜在基因组变异。材料与方法 确定了6例接受机器人前列腺切除术并完整保留前列腺的前列腺腺癌患者，这使得术前多参数MR成像与腺体之间能够进行空间映射。在每个腺体中确定了4个感兴趣区域，包括通过组织病理学分析发现正常和异常的区域。对这些空间定位的区域分别进行全外显子组DNA测序（覆盖度>50倍）。利用层次聚类、系统发育分析和主成分分析对成像和突变数据进行放射基因组学分析。结果 对6例前列腺腺癌患者（3例Gleason评分为3 + 4，3例Gleason评分为4 + 5）的23个空间不同区域进行了放射基因组多参数MR成像和全外显子组空间特征分析。层次聚类将组织病理学分析证实的高级别病变与正常区域分开，这反映了所有患者多参数MR成像与最终组织病理学分析之间的一致性。在23个空间不同的前列腺样本中，共鉴定出涉及29个癌症相关基因的77个突变。经组织病理学分析证实为正常的区域（每个样本34个突变±19个）、经多参数MR成像轻度可疑的区域（每个样本37个突变±21个）、经多参数MR成像中度可疑的区域（每个样本31个突变±15个）和高级别癌症区域（每个样本33个突变±18个）之间，癌症相关基因的突变负荷无显著差异（P = 0.30）。主成分分析区分了不同患者的样本，并进一步将Gleason评分为3 + 4与4 + 5的前列腺样本（无论组织病理学状态如何）进行了分类。结论 对腺癌前列腺进行多区域空间多参数MR成像和全外显子组放射基因组分析显示，通过组织学分析发现的高级别和正常区域的突变呈连续性。RSNA，2017 本文有在线补充材料。
