Unravelling the genetic sequences of cancer that has spread to the brain could offer unexpected targets for effective treatment, according to new research.

Researchers say that they found that the original, or primary, cancer in a patient’s body may have important differences at a genetic level from cancer that has spread to the patient’s brain (brain metastases). This insight could suggest new lines of treatment.

Dr Priscilla Brastianos, MD, a neuro-oncologist and Director of the Brain Metastasis Program at Massachusetts General Hospital, Boston, USA, said: “Brain metastases are a devastating complication of cancer. Approximately eight to ten percent of cancer patients will develop brain metastases, and treatment options are limited. Even where treatment is successfully controlling cancer elsewhere in the body, brain metastases often grow rapidly.”

Dr Brastianos and her colleagues studied tissue samples from 104 adults with cancer. In collaboration with Dr Scott Carter and Dr Gad Getz at the Broad Institute, Cambridge, USA, they analysed the genetics of biopsies taken from the primary tumour, brain metastases and normal tissues in each adult. For 20 patients, they also had access to metastases elsewhere in the body.

Brain metastases often manifest years after the primary tumour. Before this study was carried out, the extent to which the genetic profiles of brain metastases differ from that of the primary was unknown.

The researchers found that, in every patient, the brain metastasis and primary tumour shared some of their genetics, but there were also key differences. In 56% of patients, genetic alterations that potentially could be targeted with drugs were found in the brain metastasis but not in the primary tumour.

“We found genetic alterations in brain metastases that could affect treatment decisions in more than half of the patients in our study,” Dr Brastianos will say. “We could not detect these genetic alterations in the biopsy of the primary tumour. This means that when we rely on analysis of a primary tumour we may miss mutations in the brain metastases that we could potentially target and treat effectively with drugs.”

This study also found that if a patient had more than one brain metastasis, each was genetically similar.

To date, scientists have had limited understanding of how cancers change genetically, or evolve, as they spread from the primary tumour. The researchers used their findings to map the evolution of a cancer through a patient’s body, and draw up a so-called phylogenetic tree for each patient to demonstrate how the cancer had spread and where each metastasis had come from.

They concluded that brain metastases and the primary tumour share a common genetic ancestor. Once a cancer cell, or clone, has moved from the primary site to the brain, it continues to develop and amass genetic mutations. The genetic similarity of the brain metastases in individual patients suggests that each brain metastasis has developed from a single clone entering the brain.

The genetic changes in brain metastases are independent of any occurring at the same time in the primary tumour, and in metastases elsewhere in the body, the researchers said.

Characterisation of the genetics of a patient’s primary cancer can be used to optimise treatment decisions, so that drugs that target specific mutations in the cancer can be chosen. However, brain metastases are not routinely biopsied and analysed. ECC 2015

Ortho Clinical Diagnostics is emerging stronger than ever since becoming an independent company in 2014, when it was purchased by The Carlyle Group, and has made tremendous progress in developing a range of new assays. Company researchers presented data from five assays currently under development at this year’s American Association for Clinical Chemistry (AACC) meeting.

“We are investing in our business to better serve the modern clinical lab with state-of-the-art solutions,” said Ted Farrell, Vice President Business Field Assays. “We continue to enhance the quality of our products and expand our new product development pipeline for our Clinical Laboratory business.”

The assays presented at AACC address a range of important areas for clinical lab testing including HIV detection and cardiac event monitoring. Following is a quick overview:

• Ortho Clinical Diagnostics is developing a fourth generation assay to detect both HIV 1 antigen genotypes and HIV 1 & 2 antibody subgroups for use on its random access VITROS® systems. The assay demonstrated seroconversion sensitivity consistent with a commercially available fourth generation assay and was more sensitive than a third generation assay.
• A rapid, fully automated, high sensitivity assay is under development for the measurement of cardiac troponin I (cTnl) and is designed to be more analytically sensitive than contemporary cTnl and cTnT assays.
• Preliminary performance data showed that OCD’s prototype VITROS^® Insulin Assay has excellent precision, cross-reactivity with pro-insulin and c-peptide as well as good correlation with two methods that are already commercially available.
• The current VITROS^® Cl- Slide is FDA cleared for use with serum and plasma, but not in urine.Testing of urine samples using the current calibration and the proper testing protocol for plasma and serum resulted in impressive performance, reproducibility and linearity.

Ortho Clinical Diagnostics is focused on bringing targeted solutions like these to its clinical laboratory customers aimed at addressing unmet clinical needs and driving improvements to quality care. It continues to press the boundaries of what’s possible in its quest for new and better assays.  

DIAsource ImmunoAssays has received China FDA clearance for its 25OH Vitamin D ELISA assay based on proprietary (Patented) monoclonal antibodies. The test is successfully launched in the Chinese market in collaboration with a local Chinese distributor and its sub-distributors. The assay which has the CE mark and is FDA cleared, is characterized by a very simple protocol with an extremely efficient pretreatment solution directly in the ELISA well. Its extreme user-friendliness makes it a popular assay among manual ELISA users as well as in laboratories that need high throughput using open ELISA instruments. The company provides validated protocols for the most common ELISA automates in the market. This assay is one of the various assays for determination of Vitamin D (25OH Vitamin D, 1,25 (OH)2 Vitamin D and free 25OH Vitamin D) that DIAsource has available (IVD and RUO versions) in its product portfolio either in an ELISA and/or RIA format.

Rheonix Inc., a developer of fully automated molecular diagnostics solutions, has been granted patent 9,132,398, “Integrated Microfluidic Device and Methods,” for the Rheonix CARD^® cartridge, which enables assays to be performed on the company’s EncompassMDx^® and Encompass Optimum™ instruments. The CARD, which stands for Chemistry and Reagent Device, will make molecular diagnostics simpler and easier to perform through an innovative and functional design that delivers a fully automated molecular assay at a fraction of the cost of other options. All assay steps are performed within the fully enclosed cartridge, thus eliminating the potential for contamination, reducing user error, and streamlining workflow.
The CARD’s design enables adoption of advanced molecular technology by laboratories of all types, from small community hospital labs to highly complex, centralized laboratories. The design also facilitates implementation across a wide range of market opportunities, including next-generation sequencing (NGS) sample prep, research-use-only testing, food and beverage industry applications, and in vitro diagnostics.  
The ’398 patent allows researchers and clinicians to quickly, easily, and cost-effectively run several samples through a fully integrated and automated nucleic acid amplification test, from raw sample input through detection, with no user intervention. Each CARD allows for simultaneous testing of four different samples and can handle a broad range of sample types, such as fresh tissue, urine, whole blood, serum, saliva, swabs, and formalin-fixed, paraffin-embedded (FFPE) tissue. The Rheonix CARD performs multiple molecular techniques, including sample preparation, such as chemical and enzymatic lysis and DNA purification; amplification, such as endpoint polymerase chain reaction (PCR), reverse transcriptase PCR, and quantitative PCR; and detection on a low-density microarray or lateral flow strip.
“The ’398 patent recognizes the groundbreaking achievement we have reached with the Rheonix CARD. From the device’s hardware to its process, it will help make molecular diagnostics a reality in laboratories worldwide,” said Tony Eisenhut, president of Rheonix. “With the lowest cost of ownership of any molecular platform, the patent confirms the novelty of the Rheonix approach to molecular diagnostics. Where other systems have traditionally emphasized either multiplex or throughput, Rheonix has designed single-use cartridges that do both and can perform sophisticated functions with a simple design. This lowers laboratory costs by eliminating waste in time, equipment and consumables, and reduces the amount of highly skilled labour. Rheonix is helping bring powerful molecular tools to laboratories that could not previously afford to purchase or run them.”
The dual-layer design of the Rheonix CARD automatically manipulates reagents internally with its active fluidic network of pumps, valves and channels. The upper surface of the CARD contains reservoirs that hold reagents used in the extraction, purification, amplification and detection process and any resulting liquid waste. The channels and pumps located on the lower surface of the CARD are used to transport and mix reagents and move wastes into the reservoirs on the top. By actively pumping fluids from reservoir to reservoir within the CARD, molecular diagnostic tests can be performed automatically.

Cancer is a result of normal cellular functions going wildly awry on a genetic level. That fact has been known for some time, but increasing evidence is showing that the human microbiome, the diverse population of microorganisms within every person, may play a key role in either setting the stage for cancer or even directly causing some forms of it. A new study from the Perelman School of Medicine at the University of Pennsylvania, led by Erle S. Robertson, PhD and James C. Alwine, PhD, has identified, for the first time, an association between two microbial signatures and triple negative breast cancer (TNBC), the most aggressive form of the disease.

‘Viruses and other microorganisms probably have much more to do with cancer, at least the propagation of cancer and promotion of it, than is really known,’ said Alwine, a professor of Cancer Biology and associate director for core services at the Abramson Cancer Center. Using a microarray technology called PathoChip containing 60,000 molecular probes to identify all known viruses and pathogenic bacteria, fungi, parasites, and other microorganisms, Robertson, a professor of Microbiology and his colleagues screened tissue samples from 100 TNBC patients.

They also examined 40 matched and non-matched controls (matched controls are non-tumour tissue from TNBC patients; non-matched controls are breast tissue from healthy patients).

The team found a distinct microbial signature distinguishing TNBC tissue from normal samples, which could be further delineated into two broad clusters, one predominantly viral and the other predominantly bacterial, with some fungi and parasites.

‘If we look at this closely, we may also find some smaller clusters within those major groups that could give us some insights to unique identifiers for individuals in these clusters,’ stated Robertson, who is also associate director for global cancer research and co-leader of the tumour virology program at the Abramson Cancer Center. He explains that the team found ‘about 30 organisms that provide a specific type of signature to give us clues for developing a diagnostic tool.’ Co-authors Sagarika Banerjee, PhD, and Kristen Peck, from the Robertson lab, screened the organisms, and Michael Feldman, MD, PhD, and Natalie Shi from the department of Pathology and Laboratory Medicine, performed the pathology examinations to identify the TNBC cases.

Among the most prevalent viruses detected were Herpesviruses, Parapoxviruses, Retroviruses, Hepadnaviruses, Polyomaviruses, and Papillomaviruses. Significant bacterial signatures included Arcanobacterium, Brevundimonas, Sphingobacteria, and Geobacillus, while fungal species Pleistophora and Piedra and parasitic organisms Foncecaea and Trichuris were among the prominent ones identified. 

Alwine emphasizes that the detection of these and the other pathogens in TNBC tissues does not necessarily mean that they actually cause cancer. ‘There are a lot of different ways to look at this,’ he pointed out. ‘It’s possible that some of the organisms we’re looking at have a causative effect, but we don’t know that. We can’t say until it’s been thoroughly tested by many more experiments.’ One possibility is that the organisms could be adding something to the cellular microenvironment that helps damaged cells to become malignant or pushes them over the edge into cancer. Alternatively, certain organisms may simply find tumor tissue a favorable environment, without having any direct involvement at all with the cancer. ‘They might just be there because it’s a good place to hang out,’ Alwine said.

In either case, finding a distinct microbial signature associated with cancer raises the prospect of new diagnostic possibilities. ‘We’re looking at the signature as a potential for being able to diagnose cancer, possibly at an earlier stage,’ Alwine explained. Penn Medicine