A Chinese research team composed of Shenzhen Second People’s Hospital, BGI and other institutes reports their latest study on bladder cancer genomics. The discoveries were made using whole-genome and exome sequencing technologies and provide evidence that genetic alterations affecting the sister chromatid cohesion and segregation (SCCS) process may be involved in bladder tumorigenesis and open a new way for the treatment of bladder cancer.

Transitional cell carcinoma (TCC) is the most common type of bladder cancer diagnosed, accounting for 90% of all bladder malignancies in North America, South America, Europe, and Asia. It’s reported that there were an estimated 386,300 new bladder cancer cases and 150,200 deaths in 2008 alone. And the number was up to 170,000 deaths in 2010. Until now, there has been no complete genomic data available for developing new therapeutic approaches to combat bladder cancer.

To have a deeper understanding of the genetic basis underlying TCC, Chinese scientists conducted exome sequencing on the tumour and matched peripheral blood samples from 99 TCC patients, and identified 1,023 somatic substitutions and 67 indels respectively. They performed whole genome sequencing (WGS) to detect copy number alterations (CNAs) and obtained 4-fold mean haploid coverage for each sample.
After evaluating the genetic alterations or variants, researchers found frequent alterations in two genes, STAG2 and ESPL1, which are associated with the sister chromatid cohesion and segregation (SCCS) process. Among them, STAG2 was particularly notable as to harbour a greater number of non-synonymous mutations and a higher ratio of non-synonymous to synonymous mutations. Their study indicated that chromosomal instability and aneuploidy had an influence on bladder cancer, and provided evidence that bladder cancer became the first type of cancer with major genetic lesions in SCCS genes.

Furthermore, researchers detected a recurrent fusion involving two other SCCS-associated genes, FGFR3 and TACC3, by transcriptome sequencing of 42 DNA-sequenced tumors. They suggested that FGFR3/TACC3 is related with bladder tumorigenesis, and the high expression of TACC3 was mediated by transcriptional regulatory elements in the promoter of the fusion partner, FGFR3, not the amplification of TACC3. BGI

Researchers from Boston University School of Medicine (BUSM) and George Washington University (GWU) have developed a method to rapidly identify pathogenic species and strains causing illnesses, such as pneumonia, that could help lead to earlier detection of disease outbreaks and pinpoint effective treatments more quickly.
Emerging sequencing technologies have revolutionised the collection of genomic data for bioforensics, biosurveillance and for use in clinical settings. However, new approaches are being developed to analyse these large volumes of genetic data. Principal investigator Evan Johnson, PhD, assistant professor of medicine at BUSM, and Keith Crandall, PhD, director of the Computational Biology Institute at GWU, have created a statistical framework called Pathoscope to identify pathogenic genetic sequences from infected tissue samples.

This unique approach can accurately discriminate between closely related strains of the same species with little coverage of the pathogenic genome. The method also can determine the complete composition of known pathogenic and benign organisms in a biological sample. No other method can accurately identify multiple species or substrains in such a direct and automatic way. Current methods, such as the standard polymerase chain reaction detection or microscope observation, are often imperfect and time-consuming.
‘Pathoscope is like completing a complex jigsaw puzzle. Instead of manually assembling the puzzle, which can take days or weeks of tedious effort, we use a statistical algorithm that can determine how the picture should look without actually putting it together,’ said Johnson. ‘Our method can characterise a biological sample faster, more accurately and in a more automated fashion than any other approach out there.’

This work will be relevant in a broad range of scenarios. For example, in hospitals, this sequencing method will allow for rapid screening of thousands of infectious pathogens simultaneously, while being sensitive enough to monitor disease outbreaks caused by specific pathogenic strains. Veterinarians can even apply the method in their practices. This research is also applicable outside of clinical settings, allowing officials to quickly identify agents of bioterrorism (e.g. in a tainted letter) and harmful pathogens on hard surfaces, soil, water or in food products.
‘This approach has the ability to drastically change the process for identifying and combating pathogens, whether they’re in a hospital, veterinarian’s office or salmon stream,’ Crandall said. Researchers plan to conduct more studies to further verify the efficacy of their approach, and will soon begin to work with the aquaculture industry, helping fishermen with water-quality surveillance.

Washington University researchers have found that some of the same genes likely are involved in alcohol dependence and eating disorders.
Part of the risk for alcohol dependence is genetic, and the same is true for eating disorders. Now, researchers at Washington University School of Medicine in St. Louis have found it’s likely some of the same genes are involved in both.
The researchers report that people with alcohol dependence may be more genetically susceptible to certain types of eating disorders and vice versa.
‘In clinical practice, it’s been observed that individuals with eating disorders also have high rates of alcohol abuse and dependence,’ said Melissa A. Munn-Chernoff, PhD, the study’s first author. ‘Other studies have focused on the genetic connections between alcohol dependence and eating disorders, but all of those studies looked only at women. Ours was the first to include men as well.’
According to Munn-Chernoff, a postdoctoral research scholar in psychiatry, that’s important because although eating disorders tend to be thought of as a female problem, they affect men, too.
Studying data gathered from nearly 6,000 adult twins in Australia, Munn-Chernoff and her colleagues found that common genetic factors underlie alcoholism and certain eating-disorder symptoms, such as binge eating and purging habits that include self-induced vomiting and the abuse of laxatives.
By studying twins, the researchers used statistical methods to determine the odds that certain traits result from the same genes. Those statistical insights are based on the fact that identical twins share 100 percent of their genetic makeup while fraternal twins share about half.
‘By comparing the findings in identical and fraternal twins, we can develop estimates of how much of the difference in particular traits is due to genes or environment,’ Munn-Chernoff explained. ‘We found that some of the genes that influence alcohol dependence also influence binge eating in men and women.’
Even with the growing awareness and more frequent diagnoses of problems such as anorexia nervosa and bulimia nervosa, rates of the full-blown forms of these disorders are relatively low, and they’re rare in populations of twins. So the researchers surveyed study subjects about whether they suffered from eating-disorder symptoms.
‘The symptoms can cut across multiple eating disorder diagnoses,’ said Munn-Chernoff. ‘And several past studies have suggested that the particular behaviour of binge eating, as well as purging and other practices that we call compensatory behaviours, may be closely associated with alcohol dependence, which is why we focused on those symptoms.’
All of the men and women in the study were surveyed about their alcohol use and binge eating, but because the researchers were analysing data that had been gathered previously for a different study, not everyone was asked about compensatory behaviours, such as purging or using laxatives and diuretics. Only the female twins were asked about those symptoms.
In all, nearly 25 percent of the men and 6 percent of women had been alcohol dependent at some point. Almost 11 percent of these same men and 13 percent of the women had experienced problems with binge eating. In addition, about 14 percent of the women had engaged in purging or abuse of laxatives or diuretics.
On a statistical scale that runs from zero (no shared genes) to 1 (all genes shared), the researchers found that the genetic correlation between binge eating and alcohol dependence was statistically significant at .26.
Among women in the study, the genetic correlation between compensatory behaviours and alcohol dependence was significant at .32.
‘Those numbers suggest that there are shared genetic risk factors for these behaviours, such as purging and fasting,’ said Munn-Chernoff. ‘It appears that some genes that influence alcohol dependence also influence binge eating in men and women, and compensatory behaviours in women.’ Washington University School of Medicine

Miraca Holdings Inc., a Japan-based holding company in the healthcare sector, recently announced that its affiliate Innogenetics N.V. in Ghent (Belgium) had changed its name to Fujirebio Europe N.V. The name change is the next logical step in an integration process that was launched by the acquisition in September 2010 of Innogenetics N.V. by Fujirebio Inc., a subsidiary of Miraca Holdings. Fujirebio is recognized as a key player in oncology for routine and novel IVD markers. Th e name change confirms Fujirebio’s strong commitment to the introduction of the Lumipulse immunoanalyser range in laboratories across Europe. The Lumipulse G1200 was presented to the European market for the first time in Italy in November 2011 and this fully automated chemiluminescent enzyme immunoassay (CLEIA) system is now available to laboratories in Spain and will soon be available in Germany and France.

Type 2 diabetes accounts for 90 % of cases of diabetes around the world, afflicting 2.5 million Canadians and costing over 15 billion dollars a year in Canada. It is a severe health condition which makes body cells incapable of taking up and using sugar. Dr. Alexey Pshezhetsky of the Sainte-Justine University Hospital Research Center, affiliated with the University of Montreal, has discovered that the resistance to insulin seen in type 2 diabetics is caused partly by the lack of a protein that has not previously been associated with diabetes. This breakthrough could potentially help to prevent diabetes.
‘We discovered that Neu1, a protein nicknamed after ‘neuraminidase 1’, turns the absorption of sugar ‘on’ or ‘off’ in body cells, by regulating the amount of sialic acid on the surface of cells’, Dr. Pshezhetsky explains.
‘We are now trying to find a way to restore Neu1 levels and function in diabetes. If we can remove sialic acid residues from the cell surface, this will force the insulin receptor do its job of absorbing blood sugar properly. This could give doctors an opportunity to reduce the use of insulin therapy, and might help to reduce the diabetes epidemic, says Dr. Pshezhetsky.

Although type 2 diabetes is initially treated with diet, exercise and tobacco avoidance, doctors try to restore normal levels of insulin by prescribing it when this fails. The number of cases diagnosed around the world continues to grow incredibly quickly: according to the United States Center Disease Control, cases in that country grew on average by 82% between 1995 and 2010. In Oklahoma, the number increased by 226%. The disease accounts for 90% of diabetes cases around the world, and its prevalence has increased in parallel with the obesity epidemic. Obesity is in fact thought to cause this disease which can in turn lead to heart disease, strokes and even limb amputation due to poor circulation. University of Montreal