An assay that identifies a peculiar but important abnormality in cancer cells has been developed and validated by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
The assay, called OSU-SpARKFuse (Ohio State University-Spanning Actionable RNA Kinase Fusions), detects a genetic change called gene fusions in solid tumours.
Gene fusions happen when parts of two different genes join together. Gene fusions can happen, for example, when a piece of one chromosome becomes attached to another. Such chromosome “translocations” can join two genes that together become a major driver of cancer-cell and tumour growth.
Targeted therapies are becoming increasingly available that block the activity of fusion genes, particular those involving kinase genes. Whereas current assays for detecting gene fusions require previous knowledge of both genes involved in the fusion, OSU-SpARKFuse was designed to accurately detect fusions when only one of the genes is known, which allows for the discovery of novel gene fusions.
“We designed OSU-SpARKFuse to meet these needs and to identify patients who are eligible for novel therapies such as FGFR inhibitors or NTRK inhibitors that target gene fusions,” says principal investigator Sameek Roychowdhury, MD, PhD, assistant professor in the Division of Medical Oncology at Ohio State.
“Along with detecting gene fusions, OSU-SpARKFuse can provide gene-expression analysis, detect single-nucleotide changes and identify alternative splicing events and resistance genes,” says first author Julie Reeser, PhD, technical supervisor of the OSUCCC – James Cancer Genomics Laboratory.
“Additionally, OSU-SpARKFuse does not require information regarding the location of the fusion in each gene. It is an accurate, reproducible, cost-effective assay that detects gene fusions across many genes and from the small samples of tumour tissue obtained by biopsy,” Reeser adds.
The Ohio State University Comprehensive Cancer Centerhttp://tinyurl.com/yczce7e2

The European Patent Office has announced Dutch product manager Jan van den Boogaart (57) and Austrian researcher Prof. Dr. Oliver Hayden (45) as finalists for the 2017 Inventor Award in the “Industry” category. The two Siemens Healthineers employees have invented an automated method for detecting the life-threatening disease malaria. On the basis of their own research, they jointly developed a method for the Siemens Healthineers Advia 2120i hematology systembased on a combination of parameters that define whether a patient has  malaria. With this method, the Advia 2120i hematology system can run malaria tests automatically as part of a full blood panel. The great advantage is the high throughput at lower cost than with other methods, such as microscopic examination.
Until now, the most reliable method has been a microscopic examination of the blood for plasmodia, which calls for experienced, trained personnel, as recognizing plasmodia under the microscope is not easy. The process is also very time-consuming. In recent years, malaria has also been diagnosed more and more with fast tests: a test strip that detects parasite-specific antigens. But if used improperly, that test is unreliable, and it’s also expensive. www.siemens.com/press/PR2017040278HCENwww.epo.org/news-issues/press.html

Researchers at the Stanford University School of Medicine have linked chronic fatigue syndrome to variations in 17 immune-system signalling proteins, or cytokines, whose concentrations in the blood correlate with the disease’s severity.
The findings provide evidence that inflammation is a powerful driver of this mysterious condition, whose underpinnings have eluded researchers for 35 years.
“Chronic fatigue syndrome can turn a life of productive activity into one of dependency and desolation,” said Jose Montoya, MD, professor of infectious diseases, who is the study’s lead author. Some spontaneous recoveries occur during the first year, he said, but rarely after the condition has persisted more than five years.
The study’s senior author is Mark Davis, PhD, professor of immunology and microbiology and director of Stanford’s Institute for Immunity, Transplantation and Infection.
“There’s been a great deal of controversy and confusion surrounding myalgic encephalomyelitis (ME) CFS — even whether it is an actual disease,” said Davis. “Our findings show clearly that it’s an inflammatory disease and provide a solid basis for a diagnostic blood test.”
Many, but not all, ME/CFS patients experience flulike symptoms common in inflammation-driven diseases, Montoya said. But because its symptoms are so diffuse —sometimes manifesting as heart problems, sometimes as mental impairment nicknamed “brain fog,” other times as indigestion, diarrhea, constipation, muscle pain, tender lymph nodes and so forth — it often goes undiagnosed, even among patients who’ve visited a half-dozen or more different specialists in an effort to determine what’s wrong with them.
The sporadic effectiveness of antiviral and anti-inflammatory drugs has spurred Montoya to undertake a systematic study to see if the inflammation that’s been a will-o’-the-wisp in those previous searches could be definitively pinned down.
To attack this problem, he called on Davis, who helped create the Human Immune Monitoring Center. Since its inception a decade ago, the centre has served as an engine for large-scale, data-intensive immunological analysis of human blood and tissue samples. Directed by study co-author Holden Maecker, PhD, a professor of microbiology and immunology, the centre is equipped to rapidly assess gene variations and activity levels, frequencies of numerous immune cell types, blood concentrations of scores of immune proteins, activation states of intercellular signalling models, and more on a massive scale.
This approach is akin to being able to look for and find larger patterns — analogous to whole words or sentences — in order to locate a desired paragraph in a lengthy manuscript, rather than just try to locate it by counting the number of times in which the letter A appears in every paragraph.
The scientists analysed blood samples from 192 of Montoya’s patients, as well as from 392 healthy control subjects. The average age of patients and controls was about 50. Patients’ average duration of symptoms was somewhat more than 10 years.
Importantly, the study design took into account patients’ disease severity and duration. The scientists found that some cytokine levels were lower in patients with mild forms of ME/CFS than in the control subjects, but elevated in ME/CFS patients with relatively severe manifestations. Averaging the results for patients versus controls with respect to these measures would have obscured this phenomenon, which Montoya said he thinks may reflect different genetic predispositions, among patients, to progress to mild versus severe disease.
When comparing patients versus control subjects, the researchers found that only two of the 51 cytokines they measured were different. Tumour growth factor beta was higher and resistin was lower in ME/CFS patients. However, the investigators found that the concentrations of 17 of the cytokines tracked disease severity. Thirteen of those 17 cytokines are pro-inflammatory.
TGF-beta is often thought of as an anti-inflammatory rather than a pro-inflammatory cytokine. But it’s known to take on a pro-inflammatory character in some cases, including certain cancers. ME/CFS patients have a higher than normal incidence of lymphoma, and Montoya speculated that TGF-beta’s elevation in ME/CFS patients could turn out to be a link.
One of the cytokines whose levels corresponded to disease severity, leptin, is secreted by fat tissue. Best known as a satiety reporter that tells the brain when somebody’s stomach is full, leptin is also an active pro-inflammatory substance. Generally, leptin is more abundant in women’s blood than in men’s, which could throw light on why more women than men have ME/CFS.

Stanford Medicinehttp://tinyurl.com/y7agngxn

In a newly published study, Cleveland Clinic researchers have uncovered differences in the bacterial composition of breast tissue of healthy women vs. women with breast cancer. The research team has discovered for the first time that healthy breast tissue contains more of the bacterial species Methylobacterium, a finding which could offer a new perspective in the battle against breast cancer.
Bacteria that live in the body, known as the microbiome, influence many diseases.
Most research has been done on the “gut” microbiome, or bacteria in the digestive tract. Researchers have long suspected that a “microbiome” exists within breast tissue and plays a role in breast cancer but it has not yet been characterized. The research team has taken the first step toward understanding the composition of the bacteria in breast cancer by uncovering distinct microbial differences in healthy and cancerous breast tissue.
“To my knowledge, this is the first study to examine both breast tissue and distant sites of the body for bacterial differences in breast cancer,” said co-senior author Charis Eng, M.D., Ph.D., chair of Cleveland Clinic’s Genomic Medicine Institute and director of the Center for Personalized Genetic Healthcare. “Our hope is to find a biomarker that would help us diagnose breast cancer quickly and easily.  In our wildest dreams, we hope we can use microbiomics right before breast cancer forms and then prevent cancer with probiotics or antibiotics.”
The study examined the tissues of 78 patients who underwent mastectomy for invasive carcinoma or elective cosmetic breast surgery. In addition, they examined oral rinse and urine to determine the bacterial composition of these distant sites in the body.
In addition to the Methylobacterium finding, the team discovered that cancer patients’ urine samples had increased levels of gram-positive bacteria, including Staphylococcus and Actinomyces. Further studies are needed to determine the role these organisms may play in breast cancer.
Co-senior author Stephen Grobymer, M.D., said, “If we can target specific pro-cancer bacteria, we may be able to make the environment less hospitable to cancer and enhance existing treatments. Larger studies are needed but this work is a solid first step in better understanding the significant role of bacterial imbalances in breast cancer.” Dr. Grobmyer is section head of Surgical Oncology and director of Breast Services at Cleveland Clinic.

Cleveland Clinic
newsroom.clevelandclinic.org/2017/10/05/cleveland-clinic-researchers-find-link-between-bacterial-imbalances-and-breast-cancer/

An international team that just conducted the largest study of Tourette Syndrome has identified genetic abnormalities that are the first definitive risk genes for the disorder.
Although Tourette has long been thought to have a genetic basis — because the syndrome tends to appear in families — before now no definitive risk genes had been found. The breakthrough came when researchers focused on a relatively new area of genomics research that takes a broader look at the entire genome, rather than searching for a particular gene, says Peristera Paschou, Purdue University associate biology professor.
"Most times we focus on a mutation of a single base pair, which are the building blocks of DNA, and look for a mutation. But in recent years we’ve realized that there is another type of variation of the human genome," Paschou says.
Scientists have been exploring how often short sections of genes are repeated through the entire genome, how these repetitions might vary among individuals, and whether these repetitions, which are called copy number variants, have an effect on health.
"These variations may involve a large part of the DNA sequence and may even include whole genes. We have only very recently begun to understand how copy number variation may relate to disease," she says. "In the case of this research on Tourette Syndrome, we scanned the entire genome, and through physical analysis, we were able to identify where this variation lies.
"We rarely find variants that are associated at such a high level. This is why this is such a big breakthrough."
Dr. Jeremiah Scharf, of the Psychiatric & Neurodevelopmental Genetics Unit in the Massachusetts General Hospital Departments of Psychiatry and Neurology and the Massachusetts General Hospital Center for Genomic Medicine, co-senior author of the report, says this is a significant finding.
"The challenge of recognizing that Tourette Syndrome is not a single gene disorder, and that a stringent statistical certainty is required in order to declare a gene to be significantly associated with it, has been our long-term aim," he says. "We believe that what sets our study apart from prior studies is that the two genes we have identified both surpassed the stringent threshold of ‘genome-wide significance,’ and so, represent the first two definitive Tourette Syndrome susceptibility genes."

Purdue University
www.purdue.edu/newsroom/releases/2017/Q2/tourette-syndrome-risk-increases-in-people-with-genetic-copy-variations.html