scholarly journals INTEGRATIVE GENOME-WIDE ANALYSIS OF THE DETERMINANTS OF RNA SPLICING IN KIDNEY RENAL CLEAR CELL CARCINOMA

2014 ◽  
Author(s):  
KJONG-VAN LEHMANN ◽  
ANDRÉ KAHLES ◽  
CYRIAC KANDOTH ◽  
WILLIAM LEE ◽  
NIKOLAUS SCHULTZ ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Rna Splicing ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals Integrative Genome-wide Analysis of the Determinants of RNA Splicing in Kidney Renal Clear Cell Carcinoma

2014 ◽  
Author(s):  
Kjong-Van Lehmann ◽  
Andre Kahles ◽  
Cyriac Kandoth ◽  
William Lee ◽  
Nikolaus Schultz ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Alternative Splicing Events ◽  
Splicing Patterns

We present a genome-wide analysis of splicing patterns of 282 kidney renal clear cell carcinoma patients in which we integrate data from whole-exome sequencing of tumor and normal samples, RNA-seq and copy number variation. We proposed a scoring mechanism to compare splicing pat- terns in tumor samples to normal samples in order to rank and detect tumor-specific isoforms that have a potential for new biomarkers. We identified a subset of genes that show introns only observable in tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve our understanding of the underlying genetic mechanisms of splicing variation we performed a large-scale association analysis to find links between somatic or germline variants with alternative splicing events. We identified 915 cis- and trans-splicing quantitative trait loci (sQTL) associated with changes in splicing patterns. Some of these sQTL have previously been associated with being susceptibility loci for cancer and other diseases. Our analysis also allowed us to identify the function of several COSMIC variants showing significant association with changes in alternative splicing. This demonstrates the potential significance of variants affecting alternative splicing events and yields insights into the mechanisms related to an array of disease phenotypes.

scholarly journals Genome-wide Analysis of the Alternative Splicing Profiles Revealed Novel Prognostic Index for Kidney Renal Cell Clear Cell Carcinoma

2020 ◽  
Vol 11 (6) ◽  
pp. 1542-1554
Author(s):  
Li Gao ◽  
Rong-quan He ◽  
Zhi-guang Huang ◽  
Yi-wu Dang ◽  
Yong-yao Gu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Prognostic Index ◽  
Genome Wide Analysis ◽  
Genome Wide

Delayed Pancreatic Metastasis of Renal Clear Cell Carcinoma

2013 ◽  
Vol 13 (2) ◽  
pp. 79-80
Author(s):  
Zane Simtniece ◽  
Gatis Kirsakmens ◽  
Ilze Strumfa ◽  
Andrejs Vanags ◽  
Maris Pavars ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Primary Tumour ◽  
Renal Clear Cell Carcinoma ◽  
Pancreatic Metastasis ◽  
Distal Pancreatic Resection

Abstract Here, we report surgical treatment of a patient presenting with pancreatic metastasis (MTS) of renal clear cell carcinoma (RCC) 11 years after nephrectomy. RCC is one of few cancers that metastasise in pancreas. Jaundice, abdominal pain or gastrointestinal bleeding can develop; however, asymptomatic MTS can be discovered by follow-up after removal of the primary tumour. The patient, 67-year-old female was radiologically diagnosed with a clinically silent mass in the pancreatic body and underwent distal pancreatic resection. The postoperative period was smooth. Four months after the surgery, there were no signs of disease progression.

scholarly journals LncRNA CDKN2B-AS1 stabilized by IGF2BP3 drives the malignancy of renal clear cell carcinoma through epigenetically activating NUF2 transcription

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xina Xie ◽  
Jiatian Lin ◽  
Xiaoqin Fan ◽  
Yuantang Zhong ◽  
Yequn Chen ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Survival Data ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Binding Protein ◽  
Renal Clear Cell Carcinoma ◽  
Receiver Operating Curve ◽  
Migration And Invasion ◽  
Integrated Analysis

AbstractBecause of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan–Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.

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