Characterizing recurrent and lethal small renal masses in clear cell renal cell carcinoma using recurrent somatic mutations

Background and objectives: The use of non-invasive techniques to predict the histological type of renal masses can avoid a renal mass biopsy, thus being of great clinical interest. The aim of our study was to assess if quantitative multiphasic multidetector computed tomography (MDCT) enhancement patterns of renal masses (malignant and benign) may be useful to enable lesion differentiation by their enhancement characteristics. Materials and Methods: A total of 154 renal tumors were retrospectively analyzed with a four-phase MDCT protocol. We studied attenuation values using the values within the most avidly enhancing portion of the tumor (2D analysis) and within the whole tumor volume (3D analysis). A region of interest (ROI) was also placed in the adjacent uninvolved renal cortex to calculate the relative tumor enhancement ratio. Results: Significant differences were noted in enhancement and de-enhancement (diminution of attenuation measurements between the postcontrast phases) values by histology. The highest areas under the receiver operating characteristic curves (AUCs) of 0.976 (95% CI: 0.924–0.995) and 0.827 (95% CI: 0.752–0.887), respectively, were demonstrated between clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC)/oncocytoma. The 3D analysis allowed the differentiation of ccRCC from chromophobe RCC (chrRCC) with a AUC of 0.643 (95% CI: 0.555–0.724). Wash-out values proved useful only for discrimination between ccRCC and oncocytoma (43.34 vs 64.10, p < 0.001). However, the relative tumor enhancement ratio (corticomedullary (CM) and nephrographic phases) proved useful for discrimination between ccRCC, pRCC, and chrRCC, with the values from the CM phase having higher AUCs of 0.973 (95% CI: 0.929–0.993) and 0.799 (95% CI: 0.721–0.864), respectively. Conclusions: Our observations point out that imaging features may contribute to providing prognostic information helpful in the management strategy of renal masses.

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928 Targeting CAIX: Indium-111 labeled cG250 as a diagnostic tool for renal masses and lesions suspected for metastasis of clear cell renal cell carcinoma

European Urology Supplements ◽

10.1016/s1569-9056(12)60925-7 ◽

2012 ◽

Vol 11 (1) ◽

pp. e928-e928a

Author(s):

C.H.J. Muselaers ◽

E. Oosterwijk ◽

O.C. Boerman ◽

W.J.G. Oyen ◽

P.F.A. Mulders

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Diagnostic Tool ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Renal Masses ◽

Indium 111

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MP71-10 CLINICAL FEATURES OF RECURRENT SOMATIC MUTATIONS IN CLEAR CELL RENAL CELL CARCINOMA: A LARGE COHORT

The Journal of Urology ◽

10.1016/j.juro.2016.02.1456 ◽

2016 ◽

Vol 195 (4S) ◽

Author(s):

Brandon J Manley ◽

Jozefina Casuscelli ◽

Daniel M Tennenbaum ◽

Maria F Becerra ◽

Almedina Redzematovic ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Clinical Features ◽

Renal Cell ◽

Somatic Mutations ◽

Clear Cell ◽

Large Cohort ◽

Cell Renal Cell Carcinoma

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MP71-02 UTILITY OF CLEAR CELL RENAL CELL CARCINOMA GENE EXPRESSION SUBTYPES IN RISK-STRATIFYING T1 RENAL MASSES

The Journal of Urology ◽

10.1016/j.juro.2016.02.1448 ◽

2016 ◽

Vol 195 (4S) ◽

Author(s):

Aaron Laviana ◽

Amirali Salmasi ◽

Jim Hu ◽

Michael Kuo ◽

W. Rathmell ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Renal Masses

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Characterization of Hypoxia-Related Molecular Subtypes in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy and Targeted Therapy via Multi-Omics Analysis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.684050 ◽

2021 ◽

Vol 8 ◽

Author(s):

Weimin Zhong ◽

Hongbin Zhong ◽

Fengling Zhang ◽

Chaoqun Huang ◽

Yao Lin ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Renal Cell ◽

Somatic Mutations ◽

Clear Cell ◽

Molecular Subtypes ◽

Cell Renal Cell Carcinoma ◽

Cox Regression Analysis ◽

Tumor Purity

Objective: Tumor hypoxia is a key factor in resistance to anti-cancer treatment. Herein, this study aimed to characterize hypoxia-related molecular subtypes and assess their correlations with immunotherapy and targeted therapy in clear cell renal cell carcinoma (ccRCC).Materials: We comprehensively analyzed copy number variation (CNV), somatic mutation, transcriptome expression profile and clinical information for ccRCC from TCGA and ICGC databases. Based on 98 prognosis-related hypoxia genes, samples were clustered using unsupervized non-negative matrix factorization (NMF) analysis. We characterized the differences between subtypes concerning prognosis, CNV, somatic mutations, pathways, immune cell infiltrations, stromal/immune scores, tumor purity, immune checkpoint inhibitors (ICI), response to immunotherapy and targeted therapy and CXC chemokines. Based on differentially expressed genes (DEGs) between subtypes, a prognostic signature was built by LASSO Cox regression analysis, followed by construction of a nomogram incorporating the signature and clinical features.Results: Two hypoxia-related molecular subtypes (C1 and C2) were constructed for ccRCC. Differential CNV, somatic mutations and pathways were found between subtypes. C2 exhibited poorer prognosis, higher immune/stromal scores, and lower tumor purity than C1. Furthermore, C2 had more sensitivity to immunotherapy and targeted therapy than C1. The levels of CXCL1/2/3/5/6/8 chemokines in C2 were distinctly higher than in C1. Consistently, DEGs between subtypes were significantly enriched in cytokine-cytokine receptor interaction and immune responses. This subtype-specific signature can independently predict patients’ prognosis. Following verification, the nomogram could be utilized for personalized prediction of the survival probability.Conclusion: Our findings characterized two hypoxia-related molecular subtypes for ccRCC, which can assist in identifying high-risk patients with poor clinical outcomes and patients who can benefit from immunotherapy or targeted therapy.

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Comprehensive Genomic Analysis of Metastatic Non–Clear-Cell Renal Cell Carcinoma to Identify Therapeutic Targets

JCO Precision Oncology ◽

10.1200/po.18.00372 ◽

2019 ◽

pp. 1-18 ◽

Cited By ~ 2

Author(s):

Maria I. Carlo ◽

Nabeela Khan ◽

Ahmet Zehir ◽

Sujata Patil ◽

Yasser Ged ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Somatic Mutations ◽

Clear Cell ◽

De Novo ◽

Genomic Analysis ◽

Precision Oncology ◽

Single Nucleotide Variants ◽

Cell Renal Cell Carcinoma

PURPOSENon–clear-cell renal cell carcinoma (nccRCC) encompasses approximately 20% of renal cell carcinomas and includes subtypes that vary in clinical and molecular biology. Compared with clear cell renal cell carcinoma, nccRCC demonstrates limited sensitivity to conventional vascular endothelial growth factor– and mammalian target of rapamycin–directed agents, indicating a need for better therapies. Characterizing the genomic landscape of metastatic nccRCC variants may help define novel therapeutic strategies.PATIENTS AND METHODSWe retrospectively analyzed tumor tissue from patients with metastatic nccRCC who consented to genomic analysis of their tumor and germline DNA. A hybridization capture–based assay was used to identify single nucleotide variants and small insertions and deletions across more than 340 cancer-associated genes with germline comparison. Clinical actionability of somatic mutations was assessed using OncoKB levels of evidence. Microsatellite instability (MSI) in the tumor was investigated.RESULTSOf 116 patients included in the analysis, 57 (49%) presented with de novo metastatic disease, and 59 (51%) presented with localized disease that later metastasized. Subtype classifications included unclassified (n = 41; 35%), papillary (n = 26; 22%), chromophobe (n = 17; 15%), translocation associated (n = 13; 11%), and other (n = 19; 16%). Of all tumors, 15 (13%) had putative driver somatic alterations amenable to targeted therapies, including alterations in MET, TSC1/2, and an ALK translocation. Of 45 patients who had germline testing, 11 (24%) harbored mutations, seven of which could potentially guide therapy. Of 115 available tumors for analysis, two (1.7%) had high and six (5%) had intermediate MSI status.CONCLUSIONThe mutation profiles of metastatic nccRCC vary by subtype. Comprehensive analysis of somatic mutations, germline mutations, and MSI, interpreted via an annotated precision oncology knowledge base, identified potentially targetable alterations in 22% of patients, which merits additional investigation.

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