Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma

AbstractTFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.

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Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma

10.21203/rs.3.rs-296261/v1 ◽

2021 ◽

Author(s):

Guangxi Sun ◽

Junru Chen ◽

Jiayu Liang ◽

Xiaoxue Yin ◽

Mengni Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Rna Sequencing ◽

Renal Cell ◽

Angiogenesis Inhibitors ◽

Molecular Characteristics ◽

T Cell Infiltration ◽

Whole Exome ◽

Poor Outcomes ◽

Somatic Copy Number Alteration

Abstract TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer that has no standard treatment for advanced disease. We described comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion, certain fusion isoforms and high somatic copy number alteration burdens were associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibited low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis revealed five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which showed association with fusion patterns and prognosis. Specifically, the high angiogenesis/stroma/proliferation cluster exclusively consisted of tumors with ASPSCR1-TFE3 fusion, which was likely to benefit from combination of immune checkpoint and anti-angiogenesis inhibitors. Our findings reveal the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.

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Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma

Molecular Carcinogenesis ◽

10.1002/mc.23164 ◽

2020 ◽

Vol 59 (4) ◽

pp. 412-424 ◽

Cited By ~ 1

Author(s):

Takashi Tsuyukubo ◽

Kazuyuki Ishida ◽

Mitsumasa Osakabe ◽

Ei Shiomi ◽

Renpei Kato ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Copy Number ◽

Clear Cell ◽

Comprehensive Analysis ◽

Copy Number Alterations ◽

Cell Renal Cell Carcinoma ◽

Somatic Copy Number Alterations

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The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?

International Journal of Molecular Sciences ◽

10.3390/ijms22126237 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6237

Author(s):

Andrea Marchetti ◽

Matteo Rosellini ◽

Veronica Mollica ◽

Alessandro Rizzo ◽

Elisa Tassinari ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Clear Cell ◽

Treatment Algorithm ◽

Morning Glory ◽

Molecular Characteristics ◽

Cell Renal Cell Carcinoma ◽

Low Incidence

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.

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Renal cell carcinoma in children and young adults: analysis of clinicopathological, immunohistochemical and molecular characteristics with an emphasis on the spectrum of Xp11.2 translocation-associated and unusual clear cell subtypes

Histopathology ◽

10.1111/j.1365-2559.2008.03151.x ◽

2008 ◽

Vol 53 (5) ◽

pp. 533-544 ◽

Cited By ~ 62

Author(s):

A Wu ◽

L P Kunju ◽

L Cheng ◽

R B Shah

Keyword(s):

Renal Cell Carcinoma ◽

Young Adults ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Molecular Characteristics ◽

Children And Young Adults ◽

Xp11.2 Translocation

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Molecular Profiling of Druggable Targets in Clear Cell Renal Cell Carcinoma Through Targeted RNA Sequencing

Frontiers in Oncology ◽

10.3389/fonc.2019.00117 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 8

Author(s):

Corina N. A. M. van den Heuvel ◽

Anne van Ewijk ◽

Carolien Zeelen ◽

Tessa de Bitter ◽

Martijn Huynen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Rna Sequencing ◽

Renal Cell ◽

Clear Cell ◽

Molecular Profiling ◽

Cell Renal Cell Carcinoma ◽

Druggable Targets

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A prognostic nomogram based on competing endogenous RNA network for clear-cell renal cell carcinoma

10.21203/rs.3.rs-19720/v1 ◽

2020 ◽

Author(s):

Yun Peng ◽

Shangrong Wu ◽

Zihan Xu ◽

Dingkun Hou ◽

Nan Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Rna Sequencing ◽

Renal Cell ◽

Cox Regression ◽

Clear Cell ◽

Gene Signature ◽

Expression Data ◽

Competing Endogenous Rna ◽

Cell Renal Cell Carcinoma

Abstract Backgroud Clear-cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts to understand the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) were involved in the development of various tumor. However, it’s scant for studying on ccRCC, and a comprehensive analysis of prognostic model based on lncRNA-miRNA-mRNA ceRNA regulatory network of ccRCC with large-scale sample size and RNA‐sequencing expression data is still limited. Methods RNA‐sequencing expression data were taken out from GTEx database and TCGA database, A total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC-specific genes were obtained from WGCNA and differential expression analysis. Following, the communication between mRNAs and lncRNAs and target miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was constructed by univariate Cox regression, lasso methods and multivariate Cox regression analysis. Results A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dys-regulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature in cluding 8 genes based on this ceRNA was constructed, meanwhile, a nomogram predicting 1-, 3-, 5-year survival probability containing both clinical characteristics and ccRCC-specific gene signatures was developed. Conclusion It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.

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