Navigation Links
Research provides new kidney cancer clues
Date:1/19/2011

Researchers have identified a gene that is mutated in one in three patients with the most common form of renal cancer. The identification of a frequently mutated gene will provide new insights into the biology of the disease. This biological knowledge will be critical in the continued effort to improve treatment for renal cancer.

The gene called PBRM1 was found to be mutated in 88 cases out of 257 clear cell renal cell carcinomas (ccRCC) analysed, making it the most prevalent to be identified in renal cancer for 20 years. The study was carried out by researchers from the Wellcome Trust Sanger Institute, the Van Andel Research Institute, USA, and the National Cancer Centre of Singapore.

The mutations all appear to inactivate a protein which plays a role in remodelling the structure of the genetic material, allowing access of the DNA code to other proteins that can repair damage, control cell growth and turn other genes on and off.

Treating ccRCC is confounded by the fact that tumours can grow in the kidney without symptoms for some time before they are recognised. Survival rates for tumours recognised early in their development can be as high as 95 per cent, but that prognosis falls over time as tumours develop. For many years, the main genetic determinant known to be involved in the development of renal carcinoma was mutation of the VHL gene on chromosome 3.

"Until recently, when we talked about the genetics of renal carcinoma we would inevitably be talking about VHL a gene mutated in eight out of ten patients," says Dr Andy Futreal, Head of Cancer Genetics and Genomics and co-Head of the Cancer Genome Project at the Wellcome Trust Sanger Institute. "But we knew this was likely not to be the full story so the question we have sought to answer is which genes are conspiring with VHL to cause the disease we see in patients?

"Over the last year or so, we have started to assemble that puzzle this research provides a new and critical piece."

The team's recent work had previously identified three mutated genes associated with renal cancer. These genes are all involved in altering part of the scaffold known as chromatin that holds the DNA together in our cells and can influence gene activity. By altering a component of this scaffold, called a histone, the genes play a role in controlling other genes and managing how cells can divide and repair. Although these discoveries had provided a crucial glimpse of a new biological route into renal cancer, mutations in these genes only contribute in a relatively small number of cases.

Importantly, the newly discovered gene, PBRM1 (also known as Baf180), functions as part of a protein complex called SWI-SNF, which also acts to alter the structure of chromatin further pointing to the importance of genome regulation in renal cancer.

"Over the last year, our understanding of how kidney cancer develops had already markedly improved through identification of three new mutated cancer genes, each of which makes a small contribution to the disease" says Professor Mike Stratton, Director of the Sanger Institute and co-Head of the Cancer Genome Project. "Now, our discovery of PBRM1 mutations in one in three kidney cancers is a major advance. We think we may have an almost complete understanding of the set of abnormal genes that drive this cancer and our understanding of the disease has been transformed by the realisation that most of these genes are involved in providing the structure that encases DNA in the cell and that regulates its function. This insight will provide us with many new therapeutic directions for this cancer."

Much of the story, the researchers suggest, seems to be is locked into a small region of chromosome 3.The study finds that PBRM1 is tied together with two previously identified renal cancer genes including the well-established VHL cancer gene and the recently identified gene SETD2 on a small region of chromosome 3.

The team suggests that the fact that the genes are linked in their location allows cancer to exploit our biology by reducing the number of genetic events needed to hit and inactivate all three genes. The team found a significant level of overlap, with many patients carrying mutations in two, if not all three of the genes in this region.

"This study has begun to unlock the way these latest gene discoveries contribute to cancer," says Professor Bin Tean Teh from the Van Andel Research Institute, USA and National Cancer Centre of Singapore. "And it is to the cancer's advantage that they sit together. The challenge for the future will be to build a picture of the processes the genes control. That will mean looking beyond the linear DNA code to the chemical interactions that take place at the structural level at the level of the chromosome."

To begin to build a biological picture of the impact of PBRM1, the team looked at the results of experiments previously carried out in the mouse.

"By looking at the mouse, we can make the critical leap from establishing statistical association to exploring biological causation," says Dr David Adams, Head of the Experimental Cancer Genomics team at the Wellcome Trust Sanger Institute. "Our experiments in the mouse suggest that PBRM1's role as a cancer gene is not restricted to renal cancer. We find that Pbrm1 is also seen in the pancreatic cancers in the mouse.

"This finding reinforces the need to define cancer not just by the organ, but also by the mutational profile of individual patients."

As well as the PBRM1 mutations, the team also found mutations in a gene called ARID1A in some ccRCC cases. The same gene was identified just weeks ago in clear cell ovarian cancer. The researchers suggest that further larger-scale research will be needed to understand what role this second gene plays in renal cancer.


'/>"/>

Contact: Don Powell
press.officer@sanger.ac.uk
44-122-349-6928
Wellcome Trust Sanger Institute
Source:Eurekalert

Related medicine news :

1. Khalifa Foundation grants MD Anderson $150 million for cancer research
2. New European collaboration on cancer research
3. Rock concert aids cancer research
4. U-M researchers find indirect path to attack breast cancer stem cells
5. Oncology basic research director at John Theurer Cancer Center continues transplantation research
6. New research examines how HIV infections occur on the molecular level
7. Biological Psychiatry special issue: Postmortem research
8. Smoking Damages DNA Within Minutes, Research Shows
9. Researchers unzip MRSA and discover route for vaccine
10. Researchers discover way to halt lung inflammation in animal models
11. LA BioMed researchers among Americas Top Doctors
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are confused ... endometriosis. These women need a treatment plan to not only alleviate symptoms and ... help for preservation of fertility and ultimately achieving a pregnancy. The specialists at ...
(Date:6/25/2016)... ... 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due to ... a new, often overlooked aspect of head lice: the parasite’s ability to live away from ... common occurrence, but a necessary one in the event that lice have simply gotten out ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... As a ... Magna Cum Laude and his M.D from the David Geffen School of Medicine at ... returned to Los Angeles to complete his fellowship in hematology/oncology at the UCLA-Olive View-Cedars ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the benefits ... terms of the latter, setting the bar too high can result in disappointment, perhaps ... slow progress toward their goal. , Research from PsychTests.com reveals that ...
(Date:6/24/2016)... ... , ... June 19, 2016 is World Sickle Cell Observance Day. In an ... of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued a ... Cell Disease (SCD) is a disorder of the red blood cells, which can cause ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... One of Australia,s successful biotechnology ... a new biotechnology company, Noxopharm Limited [ABN 50 608 966 123] ... to list on the ASX. Noxopharm is a clinic-ready ... a Phase 1 clinical study later this year. ... the biggest problems facing cancer patients - the ability of cancers ...
(Date:6/26/2016)... Jazz Pharmaceuticals plc (Nasdaq: JAZZ ... Antitrust Improvements Act of 1976, as amended ("HSR"), with ... ("Celator"; Nasdaq: CPXX ) expired effective June ... As previously announced on May 31, 2016, Jazz ... under which Jazz Pharmaceuticals has commenced a tender offer ...
(Date:6/26/2016)... , June 27, 2016  VMS Rehab Systems, Inc. ... will take whatever measures required to build a strong ... which is currently listed on the OTC Markets-pink current ... Chairman and CEO, "We are seeing an anomaly in ... understand, not only by the Company, but shareholders and ...
Breaking Medicine Technology: