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Genomic Heterogeneity and the Small Renal Mass.

ABSTRACT: Purpose: Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors.Experimental Design: We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as small (<4 cm) and large (>7 cm) tumors. Each tumor had three regions sampled. Copy-number variation (CNV) was assessed and gene expression analysis was performed to characterize the clear-cell A and B (ccA/ccB) profile and the cell-cycle progression (CCP) score. Genomic heterogeneity between three regions was evaluated using CNV subclonal events, regional expression profiles, and correlation between gene expression.Results: Twenty-three small and 24 large tumors were analyzed. Total CNVs and subclonal CNVs events were less frequent in small tumors (P < 0.001). Significant gene expression heterogeneity was observed for both CCP scores and ccA/ccB classifications. Larger tumors had more variance in CCP scores (P = 0.026). The distribution of ccA/ccB differed between small and large tumors with mixed ccA/ccB tumors occurring more frequently in the larger tumors (P = 0.024). Analysis of five mixed tumors (with both ccA/ccB regions) demonstrated the more aggressive ccB phenotype had greater CNV events (P = 0.014).Conclusions: Small renal tumors have much less genomic complexity and fewer subclonal events. Pretreatment genomic characterization with single-needle biopsy in small tumors may be useful to assess biologic potential and may influence therapy. Clin Cancer Res; 24(17); 4137-44. ©2018 AACR.

SUBMITTER: Ueno D

PROVIDER: S-EPMC6125159 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Genomic Heterogeneity and the Small Renal Mass.

Ueno Daiki D Xie Zuoquan Z Boeke Marta M Syed Jamil J Nguyen Kevin A KA McGillivray Patrick P Adeniran Adebowale A Humphrey Peter P Dancik Garrett M GM Kluger Yuval Y Liu Zongzhi Z Kluger Harriet H Shuch Brian B

Clinical cancer research : an official journal of the American Association for Cancer Research 20180514 17

<b>Purpose:</b> Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors.<b>Experimental Design:</b> We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as ...[more]

PMID: 29760223

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Project description:PurposeThis study seeks to evaluate the use of quantitative texture parameters extracted from multiphasic contrast-enhanced magnetic resonance (MR) imaging in differentiating between benign and malignant masses (oncocytoma vs. clear cell and papillary RCC) and between common subtypes of renal cell carcinoma (clear cell vs. papillary RCC) in small renal masses (< 4 cm).MethodOne-hundred and forty-two renal lesions (90 clear cell and 22 papillary RCCs; 30 oncocytomas) were identified in a cohort of 41 patients (18 men, 23 women: mean age, 52.8 ± 14.4 years) who underwent preoperative multiphasic contrast-enhanced MR with four phases (unenhanced, arterial, venous, and delayed) between 2015 and 2016. In this study, texture features were extracted from entire cross-sectional tumoral region in three consecutive slices containing the largest cross-sectional area from each of the four phases. The change in imaging feature between precontrast imaging and each postcontrast phase was calculated. Data dimension reduction and feature selection were performed by conducting (1) pairwise Wilcoxon rank test followed by modified false discovery rate adjustment, and (2) Lasso regression. Multivariate modeling incorporating the selected features was performed using random forest classification method.ResultsHistogram imaging features were informative variables in differentiating between benign and malignant masses, while textures imaging features were of added value in differentiating between subtypes of RCCs. Papillary RCCs were distinguished from clear cell RCCs (sensitivity 65.5%, specificity 88%, and accuracy 77.9%), oncocytomas from clear cell RCCs (sensitivity 67.3%, specificity 88.9%, and accuracy 79.3%), and oncocytomas from papillary and clear cell RCCs (sensitivity 64.7%, specificity 85.9%, and accuracy 77.9%).ConclusionsA combination of histogram and texture imaging features on multiphasic MR can help differentiate histologic cell types in common small renal masses (< 4 cm).

Dataset Information

Genomic Heterogeneity and the Small Renal Mass.

Publications

Genomic Heterogeneity and the Small Renal Mass.

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