Navigation Links
BGI reports study results on frequent mutation of genes encoding UMPP components in kidney cancer
Date:12/4/2011

December 4th, 2011, Cambridge, MA and Shenzhen, China BGI, the world's largest genomics organization, announced that a study on frequent mutation of genes encoding ubiquitin-mediated proteolysis pathway (UMPP) components in clear cell renal cell carcinoma (ccRCC) is published online today in Nature Genetics. In addition to BGI, co-leaders of the study included Peking University Shenzhen Hospital, Shenzhen Second People's Hospital, among others. The study reveals that alteration of UMPP may contribute to ccRCC by activation of the hypoxia regulatory network, providing new clues to trace the key molecular mechanisms and pathways that underlie the tumorigenesis and progression of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of kidney cancer, with 102,000 deaths worldwide each year. It is characterized by high metastatic potential and poor prognosis. Up to 40% of patients have disease recurrence after nephrectomy. In this study, the research team specifically looked at alterations in ubiquitin-mediated proteolysis pathway and studied its potential impacts linked to ccRCC tumorigenesis. The UMPP has been reported to be associated with many diseases including cancer and plays a critical role in the protein metabolism as a major pathway for protein degradation in cells.

"Adding to the previous research effort of transitional cell carcinoma in bladder cancer published in Nature Genetics earlier this year, we and our partners continued our study of strongly aggressive ccRCC tumors to identify the mutated genes associated with the process of tumorigenesis," said Guangwu Guo, one of the co-leading authors of the study and PI of this project at BGI. "The new discoveries in this study led us to a remarkable step in our understanding of the genetic landscape of ccRCCs and toward potential treatment against this aggressive tumor."

To gain a deep insight into the genetic basis of ccRCC, researchers analyzed ten primary tumors with matched morphologically normal renal tissues utilizing the whole exome sequencing approach on BGI's sequencing platform. The mutation prevalence was estimated by screen of ~1,100 genes with somatic mutations or that have been causally implicated in cancers in 88 additional ccRCCs for prevalence screen.

There were 23 significantly mutated genes identified in the 98 ccRCCs, including the five well-known renal cancer genes such as VHL and TP53, and genes involved in chromatin modification such as PBRM1, JARID1C and SETD2. "We have identified 12 genes which were previously unknown to be involved in ccRCC, including two tumor suppressor genes, BAP1 and TSC1. Integration of previous studies and our findings suggest that some of the genes may play important roles in ccRCC genesis," said Guo.

In addition to the attempt to identify all mutated genes associated with ccRCC, researchers also focused on specific genes, pathways and mechanisms that potentially play a key role in ccRCC tumorgenesis and warrant exploration as potential targets for treatments. One of the targets was mutations in VHL gene that were commonly suggested to be involved in ccRCC genesis in many previous genetic studies with reported prevalence ranging between 50% and 80%. Interestingly, researchers have found a much lower prevalence of 27% in this study. VHL promoter hypermethylation was only found in 6% of the tumors relative to their matched normal samples, also suggesting a lower prevalence of epigenetic VHL alternation, according to the researchers.

Although the alteration of VHL gene is widely known for its association with kidney cancer, researchers also revealed the frequent mutation of UMPP linked to ccRCC in this study and have sequenced all 135 genes in UMPP in the prevalence screen. A significantly high mutation frequency of UMPP was found in the 98 carcinoma samples. The pathway analysis suggested that alternation of UMPP could potentially play an important role in ccRCC tumorigenesis, and it may contribute by activating the hypoxia regulatory network.

"This study has enhanced our knowledge and laid an important foundation for future research of ccRCC. The new discovery on the potential contribution of UMPP to ccRCC justifies more comprehensive investigation of this pathway, including proteomics research of the protein network to fully elucidate its role in ccRCC genesis," said Professor Jun Wang, Executive Director of BGI.


'/>"/>

Contact: Jia Liu
liujia@genomics.cn
BGI Shenzhen
Source:Eurekalert

Related biology news :

1. Genetic Engineering & Biotechnology News reports on growing role of molecular diagnostics
2. GEN reports on novel tools for deciphering biological networks
3. Synaptics Reports Record Results for First Quarter of Fiscal 2009
4. Communication Intelligence Corporation Reports Third Quarter 2008 Financial Results
5. Orchid Cellmark Reports Third Quarter 2008 Financial Results
6. Genetic Engineering & Biotechnology News reports on the trend toward predictive toxicogenomics
7. GEN reports growing focus on PI3-kinase pathway in cancer research
8. Cytori reports benefit of adipose-derived regenerative cells in spinal disc model
9. GEN reports on growing reliance on microfluidics technology
10. GEN reports on strategies to overcome blood-brain barrier
11. Aware, Inc. Reports Fourth Quarter and 2008 Financial Results
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/22/2016)... -- On Monday, the Department of Homeland Security (DHS) ... for the Biometric Exit Program. The Request for Information ... explains that CBP intends to add biometrics to confirm ... States , in order to deter visa overstays, ... Logo - http://photos.prnewswire.com/prnh/20160622/382209LOGO ...
(Date:6/15/2016)... , June 15, 2016 ... market report titled "Gesture Recognition Market by Application Market - Global ... 2016 - 2024". According to the report, the  global ... billion in 2015 and is estimated to grow ... 48.56 billion by 2024.  Increasing application ...
(Date:6/3/2016)... 3, 2016 Das ... Nepal hat ein 44 ... geprägter Kennzeichen, einschließlich Personalisierung, Registrierung und IT-Infrastruktur, ... Produktion und Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte ... Januar teilgenommen, aber Decatur wurde als konformste ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Global demand for enzymes ... through 2020 to $7.2 billion.  This market includes ... cleaning products, biofuel production, animal feed, and other ... and biocatalysts). Food and beverages will remain the ... increasing consumption of products containing enzymes in developing ...
(Date:6/27/2016)... ... June 27, 2016 , ... Parallel 6 , the leading ... the Clinical Reach Virtual Patient Encounter CONSULT module which enables both audio ... and clinical trial team. , Using the CONSULT module, patients and physicians can schedule ...
(Date:6/27/2016)...   Ginkgo Bioworks , a leading organism ... today awarded as one of the World Economic ... most innovative companies. Ginkgo Bioworks is engineering biology ... world in the nutrition, health and consumer goods ... customers including Fortune 500 companies to design microbes ...
(Date:6/24/2016)... ... ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical journal ... Their findings are the subject of a new article on the Surviving Mesothelioma website. ... the blood, lung fluid or tissue of mesothelioma patients that can help point doctors ...
Breaking Biology Technology: