Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

BGI reports study results on frequent mutation of genes encoding UMPP components in kidney cancer

05.12.2011
Study published online today in Nature Genetics

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.

About BGI

BGI was founded in Beijing, China, in 1999 with the mission to become a premier scientific partner for the global research community. The goal of BGI is to make leading-edge genomic science highly accessible, which it achieves through its investment in infrastructure, leveraging the best available technology, economies of scale, and expert bioinformatics resources. BGI, and its affiliates, BGI Americas, headquartered in Cambridge, MA, and BGI Europe, headquartered in Copenhagen, Denmark, have established partnerships and collaborations with leading academic and government research institutions as well as global biotechnology and pharmaceutical companies, supporting a variety of disease, agricultural, environmental, and related applications.

BGI has a proven track record of excellence, delivering results with high efficiency and accuracy for innovative, high-profile research: research that has generated over 170 publications in top-tier journals such as Nature and Science. BGI's many accomplishments include: sequencing one percent of the human genome for the International Human Genome Project, contributing 10 percent to the International Human HapMap Project, carrying out research to combat SARS and German deadly E. coli, playing a key role in the Sino-British Chicken Genome Project, and completing the sequence of the rice genome, the silkworm genome, the first Asian diploid genome, the potato genome, and, more recently, have sequenced the human Gut Metagenome, and a significant proportion of the genomes for the1000 Genomes Project. For more information about BGI, please visit www.genomics.cn or www.bgiamericas.com.

Contact Information:

Guangwu Guo, Ph.D.
Group Leader of Cancer Genome Analysis,
BGI
guogw@genomics.cn
www.genomics.cn
Joyce Peng, Ph.D.
Marketing Director
BGI Americas
626-222-5584
joyce.peng@bgiamericas.com
www.bgiamericas.com
Bicheng Yang, Ph.D.
Public Communication Officer
BGI
+86-755-82639701
yangbicheng@genomics.cn

Jia Liu | EurekAlert!
Further information:
http://www.genomics.cn

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>