Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study sheds light on genetic architecture of kidney cancer

29.10.2014

Research reveals link between renal cell carcinoma and exposure to aristolochic acid

A new study on a large cohort of kidney cancer patients in Europe sheds light on the genetic architecture of the disease -- and reveals an apparent link between exposure to aristolochic acid and incidence of kidney cancer, particularly in Romania.

The research, by an international team led by scientists from the McGill University and Genome Quebec Innovation Centre in Montreal, underscores the importance of investigating possible sources of exposure to aristolochic acid. The compound, found in plants of the Aristolochia genus, also has been suspected of causing a kidney disease known as Balkan endemic nephropathy, affecting people along the tributaries of the Danube River in Croatia, Bosnia and Herzegovina, Serbia, Bulgaria and Romania. Aristolochia clematitis, or European birthwort, is a common plant throughout the Balkans.

Results of the study, which focused on the most common form of kidney cancer – clear-cell renal cell carcinoma -- are reported today (Oct. 29) in Nature Communications. Renal cancer accounts for 2.4% of all adult cancers and more than 140,000 deaths annually. Incidence rates have been increasing sharply, with the highest rates occurring in Central Europe.

The researchers performed whole-genome sequencing on DNA isolated from blood and tumour tissue samples and RNA sequencing on tumour and matched normal tissue samples taken from a total of 94 kidney-cancer patients in four countries: the Czech Republic, Romania, Russia and the United Kingdom.

"The most striking observation was the high frequency of a specific type of mutation pattern found in the Romanian patients," says Yasser Riazalhosseini, an assistant professor of genetics at McGill. "The specific sequence context surrounding these mutations and their predominance on the non-transcribed strand of DNA enabled us to hypothesize that the mutation is due to exposure to aristolochic acid during the patient's lifetime."

This same mutation pattern is found in patients suffering from urinary-tract cancer associated with Balkan endemic nephropathy. That disease is thought by many scientists to be due to consumption of wheat flour contaminated with seeds of Aristolochia clematitis. Aristolochic acid is also used in herbal remedies in parts of Asia.

"While the study included only 14 patients from Romania, the specific mutation pattern was found in 12 of them. As a result, we will analyze samples from more patients from Romania and elsewhere in the Balkan region, in follow-up research that is now underway to assess the extent of exposure," says Professor Mark Lathrop, scientific director of the McGill University and Genome Quebec Innovation Centre, who led the study.

The broader results reported today also confirm that a certain signalling pathway, called PI3K/mTOR, is significantly deregulated in kidney cancer. The study further reveals that a connected pathway, called focal adhesion, is affected by molecular aberrations in many patients. "This finding adds to evidence that targeted therapies for PI3K/mTOR signaling may be applied effectively to kidney cancer, and may help patients affected by abnormalities of the focal adhesion pathway, as well," Riazalhosseini says.

The study was conducted under the Cancer Genomics of the Kidney (CAGEKID) program as part of the International Cancer Genome Consortium (ICGC). The CAGEKID program is led by Mark Lathrop, and collaborating institutions involved in the study include the International Agency for Research on Cancer and the Centre National de Génotypage in France, Cancer Research UK Centre, St James's University Hospital, Leeds and the European Bioinformatics Institute in the UK.

"This tumour genomic project is unique in that it is based on samples from various countries, with potential diversity in risk factors," says Ghislaine Scelo of the International Agency for Research on Cancer. "Our study illustrates that systematic exploration of tumour DNA via massive sequencing can identify previously unsuspected causes of cancer."

###

Funding for the research was provided by the EU FP7 program, Génome Quebec, le Ministère de l'Enseignement supérieur, de la Recherche, de la Science et de la Technologie Québec and McGill University.

"Variation in genomic landscape of clear cell renal cell carcinoma across Europe," by Scelo, Riazalhosseini, et al. Nature Communications, published Oct. 29, 2014.
DOI: 10.1038/ncomms6135

Chris Chipello | Eurek Alert!
Further information:
http://www.mcgill.ca/

More articles from Studies and Analyses:

nachricht Do microplastics harbour additional risks by colonization with harmful bacteria?
05.04.2018 | Leibniz-Institut für Ostseeforschung Warnemünde

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

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: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

Im Focus: Stronger evidence for a weaker Atlantic overturning

The Atlantic overturning – one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards – is weaker today than any time before in more than 1000 years. Sea surface temperature data analysis provides new evidence that this major ocean circulation has slowed down by roughly 15 percent since the middle of the 20th century, according to a study published in the highly renowned journal Nature by an international team of scientists. Human-made climate change is a prime suspect for these worrying observations.

“We detected a specific pattern of ocean cooling south of Greenland and unusual warming off the US coast – which is highly characteristic for a slowdown of the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Improved stability of plastic light-emitting diodes

19.04.2018 | Power and Electrical Engineering

Enduring cold temperatures alters fat cell epigenetics

19.04.2018 | Life Sciences

New capabilities at NSLS-II set to advance materials science

18.04.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>