Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Spanish researchers sequence non-infiltrating bladder cancer exome

14.10.2013
The study's authors identify new genetic pathways and new genes involved in bladder cancer; The genetic signature of these patients is a first step towards understanding the biology of this illness and improving patient management

Bladder cancer represents a serious public health problem in many countries, especially in Spain, where 11,200 new cases are recorded every year, one of the highest rates in the world.


This image shows a bladder tumor sample containing mutations in the STAG2 gene.

Credit: CNIO

The majority of these tumours have a good prognosis -- 70-80% five-year survival after diagnosis -- and they do not infiltrate the bladder muscle at the time of diagnosis -- in around 80% of cases.

Despite this, many of the tumours recur, requiring periodic cytoscopic tumour surveillance. This type of follow-up affects patients' quality of life, at the same time as incurring significant healthcare costs.

Researchers at the Spanish National Cancer Research Centre (CNIO), coordinated by Francisco X. Real, head of the Epithelial Carcinogenesis Group and Nuria Malats, head of the Genetic & Molecular Epidemiology Group, have carried out the first exome sequencing for non-infiltrating bladder cancer, the most frequent type of bladder cancer and the one with the highest risk of recurrence (the exome is the part of the genome that contains protein synthesis information).

The results reveal new genetic pathways involved in the disease, such as cellular division and DNA repair, as well as new genes -- not previously described -- that might be crucial for understanding its origin and evolution.

"We know very little about the biology of bladder cancer, which would be useful for classifying patients, predicting relapses and even preventing the illness", says Cristina Balbás, a predoctoral researcher in Real's laboratory who is the lead author of the study.

The work consisted of analysing the exome from 17 patients diagnosed with bladder cancer and subsequently validating the data via the study of a specific group of genes in 60 additional patients.

"We found up to 9 altered genes that hadn't been described before in this type of tumour, and of these we found that STAG2 was inactive in almost 40% of the least aggressive tumours", says Real.

The researcher adds that: "Some of these genes are involved in previously undescribed genetic pathways in bladder cancer, such as cell division and DNA repair; also, we confirmed and extended other genetic pathways that had previously been described in this cancer type, such as chromatin remodelling".

AN UNKNOWN AGENT IN BLADDER CANCER

The STAG2 gene has been associated with cancer just over 2 years ago, although "little is known about it, and nothing about its relationship to bladder cancer", says Balbás. Previous studies suggest it participates in chromosome separation during cell division (chromosomes contain the genetic material), which is where it might be related to cancer, although it has also been associated with maintenance of DNA´s 3D structure or in gene regulation.

Contrary to what might be expected, the article reveals that tumours with an alteration in this gene frequently lack changes in the number of chromosomes, which indicates, according to Real, that "this gene participates in bladder cancer via different mechanisms than chromosome separation".

The authors have also found, by analysising tumour tissue from more than 670 patients, that alterations in STAG2 are associated, above all, with tumours from patients with a better prognosis.

How and why these phenomena work still needs to be discovered but the researchers predict that "mutations in STAG2 and other additional genes that we showed to be altered could provide new therapeutic opportunities in some patient sub-groups".

The research project was carried-out in close collaboration with other CNIO groups and units, including the Chromosome Dynamics Group, led by Ana Losada, the Computational & Structural Biology Group, led by Alfonso Valencia, the Molecular Cytogenetics Group, led by Juan Cruz Cigudosa, as well as the Genomics Unit, headed by Orlando Domínguez, and the Bioinformatics Unit, led by David Pisano. The National Genome Analysis Centre (CNAG) and the Hospital del Mar's Urology Service in Barcelona have also played an important role in the project, as have other Spanish hospitals and universities.

Acknowledgements: this work has been made possible thanks to the support of the Spanish Ministry of Economy & Competitiveness, the National Institute of Health Carlos III, the Spanish Association Against Cancer (AECC), the "la Caixa" Foundation, the Banco Santander Foundation, the European Union's 7th Framework Programme and the National Institute of Health in the US.

Reference article:

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Cristina Balbás-Martínez, Ana Sagrera, Enrique Carrillo-de-Santa-Pau, Julie Earl, Mirari Márquez, Miguel Vazquez, Eleonora Lapi, Francesc Castro-Giner, Sergi Beltran, Mònica Bayés, Alfredo Carrato, Juan C Cigudosa, Orlando Domínguez, Marta Gut, Jesús Herranz, Núria Juanpere, Manolis Kogevinas, Xavier Langa, Elena López-Knowles, José A Lorente, Josep Lloreta, David G Pisano, Laia Richart, Daniel Rico, Rocío N Salgado, Adonina Tardón, Stephen Chanock, Simon Heath, Alfonso Valencia, Ana Losada, Ivo Gut, Núria Malats, Francisco X Real. Nature Genetics (2013). DOI: 10.1038/ng.2799

Nuria Noriega | EurekAlert!
Further information:
http://www.cnio.es

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>