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Pathway Genomics to Launch Next-Generation Sequencing (NGS) Comprehensive Cancer Panel Including BRCA1 and BRCA2

Pathway Genomics, a genetic testing laboratory on the forefront of bringing physicians a broad genetic testing portfolio covering a wide range of diseases, announces the pending launch of its inherited cancer panel with BRCA1 and BRCA2.

Pathway Genomics’ Hereditary Cancer DNA Insight test utilizes next-generation sequencing (NGS) technology and will analyze genes related to a selection of hereditary cancers including breast, ovarian, colorectal and others. The company notes that it intends to introduce all their cancer panels in August 2013.

“I am delighted to see laboratories like Pathway offering genetic tests for inherited cancers,” said Linda Wasserman, M.D., Ph.D., former Director of the Clinical Cancer Genetics Care Unit at Moores UCSD Cancer Center. “Next-generation sequencing is a critical step in making actionable genetic information more accessible to the physician, ultimately benefitting the patient.”

Inherited BRCA gene mutations are responsible for approximately five percent of breast cancers and about 10-15% of ovarian cancers. Patients who have deleterious BRCA mutations may also have increased risk of other cancers.

Jim Plante, President and CEO of Pathway said, “Pathway is committed to innovation in health care and to improving the health of millions of patients with increased risk of developing cancer. We believe Pathway Genomics’ Hereditary Cancer DNA Insight is an important test in our genetic portfolio and it will enable the medical community to progress towards more personalized health care at an affordable price.”

Pathway Genomics’ genetic tests screen patient DNA using advanced technologies to provide scientifically-validated and actionable information for a wide range of genetic and inherited diseases including recessive diseases, traits that impact heart health, drug response and nutrition.

Source: Pathway Genomics

Cancer Research UK and CRT Collaborate with Abcodia to Discover and Develop Tests for Early Diagnosis of Cancer

Cancer Research UK and its commercial arm, Cancer Research Technology (CRT), have joined forces with Abcodia, the biomarker validation company with a focus on cancer screening, to develop new blood tests to detect a range of cancers when they are still at a very early stage.

The strategic alliance will focus on biomarkers to detect cancers before patients develop symptoms, concentrating on cancers which currently have limited screening tests available, such as non-small cell lung cancer.

Detecting cancer earlier will give doctors the best chance to treat cancer effectively, before the disease develops and spreads when it becomes more difficult to treat. Identifying patients at an early stage will also provide the scientific and pharmaceutical communities with the ability to select patients for the development of a new generation of anti-cancer medicines.

The partnership combines Cancer Research UK’s extensive clinical oncology and scientific network with Abcodia’s expertise in the longitudinal profiling of biomarkers, as well as its exclusive access to one of the world’s largest prospective collections of serum samples available for biomarker research. This collection is derived from the UK Collaborative trial for Ovarian Cancer Screening* (UKCTOCS) run at University College London (UCL) and contains more than five million serum samples. The trial is part funded by Cancer Research UK.

The samples in the collection have been taken from healthy people annually and in many cases, up to 10 years prior to a cancer diagnosis. The collaboration will use these samples to select biomarkers which provide a clear indication of change in the early pre-diagnosis stages of disease.

Cancer Research UK, CRT and Abcodia will seek partnerships in the UK and internationally, with academic and commercial organisations which have leading-edge biomarker technology, to discover, validate and further develop the markers.

Dr Julie Barnes, Abcodia’s CEO, said: “We are delighted to be able to work with Cancer Research UK and CRT in this new global venture. The early diagnosis of cancer has never been more important and with the collective expertise that this alliance can bring, we hope to make a real difference in the field of early cancer detection and screening.”

The alliance is particularly interested in seeking markers that may be expressed in serum; for example, proteins, microRNAs – regulators of gene expression, exosomes ¬– cell-derived vesicles, autoantibodies – antibodies targeting an individual’s own proteins, and DNA methylation – a molecular switch to turn DNA on and off. Both genetic and acquired risk factors will also be investigated.

Abcodia and CRT will jointly commercialise any biomarkers discovered during the collaboration and share revenues resulting from potential licensing deals with additional third parties.

Dr Harpal Kumar, Cancer Research UK’s chief executive, said: “Earlier detection of cancer remains a huge challenge but also a tremendous opportunity. We know that for most types of cancer, the earlier we detect them, the greater the chance of being able to treat them effectively and successfully. Furthermore, treating earlier stage disease is usually associated with fewer side effects from treatment for our patients. The scope and scale of this alliance, aimed at developing new tests for a range of cancers at their earliest stage, before symptoms develop, is very exciting. The combination of expertise formed by this partnership provides a great opportunity to accelerate this vital biomarker research, which we hope will help save thousands of lives from cancer.”

Professor Ian Jacobs, Vice President at the University of Manchester, Principle Investigator of UKCTOCS and an Abcodia founder, said: “I’m delighted that the biobank developed through UKCTOCS will be used for such an important collaborative venture which has potential to yield important discoveries and to benefit patients through early detection across a range of cancers.”

Dr Keith Blundy, Cancer Research Technology’s chief executive, said: “This important alliance combines Cancer Research UK’s clinical expertise, with the commercialisation expertise of both Abcodia and CRT. Together with additional technology partners, we hope to be able to identify early detection biomarkers that will enable patients to be treated as soon as possible, ultimately saving lives.”

Source: Abcodia

Biomarker Identification May Lead to New Noninvasive Test for Colorectal Cancer Detection

The average 5-year survival for colorectal cancer (CRC) is less than 10% if metastasis occurs, but can reach 90% if detected early. A new non-invasive test has been developed that measures methylation of the SDC2 gene in tissues and blood sera. This test detected 87% of all stages of colorectal cancer cases (sensitivity) without significant difference between early and advanced stages, while correctly identifying 95% of disease-free patients (specificity). The results are published in the July issue of The Journal of Molecular Diagnostics.

According to the US Centers for Disease Control and Prevention, CRC is the second leading cancer killer in the US affecting both men and women. In 2009, close to 137,000 people in the US were diagnosed with CRC, with close to a 40% mortality rate.

There are other screening choices for CRC, including fecal occult blood testing (FOBT), fecal immunochemical testing, and colonoscopy. Colonoscopy is the gold standard of CRC screening, but patient resistance – mostly due to the unpleasant preparation – has curbed widespread adoption. FOBT is non-invasive but has limited sensitivity, particularly for early disease. A sensitive and specific non-invasive test using blood or stool could to be a more preferable option with the potential of saving many lives.

In their search for a biomarker that could be used for the early detection of CRC, investigators from Genomictree, Inc. and Yonsei University College of Medicine in Seoul, South Korea, performed DNA microarray analysis coupled with enriched methylated DNA using tissues from primary tumors and non-tumor tissues from 12 CRC patients. After step-wise filtering, they found a set of genes that were highly methylated across all of the CRC tumors. Ultimately they identified one gene, SDC2, which encodes the membrane syndecan-2 protein, a protein that is known to participate in cell proliferation, cell migration, and is expressed in colon mesenchymal cells. The methylation level of target region of SDC2 assessed in tumor tissue was found to be significantly higher than that from paired adjacent non-tumor tissue.

The next step was to clinically validate the biomarker by analyzing SDC2 methylation levels in primary tumors and paired-adjacent non-tumor tissue samples from 133 CRC patients. Investigators found that in the transcriptional regulatory region of the SDC2 gene, tumor samples showed significantly higher levels of methylation than the control samples. SDC2 methylation positivity ranged from 92.9% to 100% when samples were stratified according to stages of cancer.

Further, investigators found that the SDC2 biomarker could be measured in serum samples from CRC patients and healthy individuals. “The SDC2 methylation test was able to detect 92% for detection of stage I cancer patients indicating that SDC2 is suitable for early detection of CRC where therapeutic interventions have the greatest likelihood of curing the patient from the disease,” says first author TaeJeong Oh, PhD.

The authors suggest that the SDC2 methylation test they describe could possibly be used as an alternative to or in conjunction with colonoscopy. It could also be used to monitor cancer progression and treatment. Dr. Sungwhan An, corresponding author and CEO of Genomictree, Inc., commented: “We are very excited with this result using a small amount of serum DNA from less than 1ml of blood. I believe a greater volume of blood will further improve the clinical performance of this test. We are currently preparing another set of clinical validation studies evaluating SDC2 methylation in serum DNA from patients with early adenoma.” In future research the authors will explore whether this biomarker is specific to CRC or universal among other cancers.

Source: Gnome-Wide Identification and Validation of a Novel Methylation Biomarker, SDC2, for Blood-Based Detection of Colorectal Cancer

Source: EurekAlert!

Early Indicators of Lung Cancer Probed in New Study

Many of the critical processes underlying cancer formation and eventual metastasis to other organs remain mysterious. In the quest for earlier diagnoses and more effective treatment, intensive research efforts have been applied to the search for biomarkers—presymptomatic signs of disease detectable in blood, saliva, or other biofluids.

Chad Borges, an analytical biochemist working at Arizona State University’s Biodesign Institute has been studying a particularly promising class of potential biomarkers known as glycans. His new study, appearing in the journal Analytical Chemistry, investigates the formation of aberrant glycan molecules, which have been clinically implicated in a range of deadly cancers including ovarian, prostate, pancreatic, liver, multiple myeloma, breast, lung, gastric, thyroid and colorectal.

Indeed, as the authors note, nearly every known type of tumor cell displays abnormal glycans, making them a particularly attractive candidate for biomarker discovery and validation. Until now, however, detecting the source of aberrant glycans has been frustratingly difficult.

Borges is a member of Biodesign’s Molecular Biomarkers Unit, where proteins and protein modifications are examined for their potential as markers of human disease. “Our primary work has to do with extracting proteins from blood samples or other biofluids, purifying them and examining them in an intact state through mass spectrometry,” Borges says. “We look for variants in these proteins, which in many cases include glycosylation—the focus of this paper—except in this case we looked at global changes across all blood serum proteins.”

Glycans are biological sugar polymers, made up of several different types of sugar units—glucose, mannose, galactose and others. Glycans typically adorn the surfaces of cells and can act to modify proteins. Unlike other biological polymers like DNA and proteins, however, glycans are made “on-the-go,” without a preset template. This makes their formation and behavior trickier to predict.

As Borges explains, “glycans are assembled by enzymes through a first come, first build process. In cancer, the protein enzymes that form glycans—known as glycotranserases—get overexpressed. When that happens, you get these weird glycan structures that aren’t normal.” The study found, for the first time, at least two glycotransferases displaying aberrant activity in lung cancer samples, with other abnormal glycotransferase activity strongly implied as well.

The assembly of glycans is schematically similar to a tinker toy set in which glycotransferase enzymes act to connect various wheel-like sugar units via spoke-like branching elements. Overexpression of glycotransferases produces aberrant glycans, which tend to display bushier, more profuse branching patterns when compared with their normal counterparts. (see Figure 1).

These abnormal glycans can help facilitate metastasis of cancerous cells, because their presence on cell surfaces is differentially recognized by the immune system. Instead of destroying diseased cells, the immune system leaves them alone. The abnormal glycans can also help cancer cells traverse non-native tissues, i.e. metastasize.

In the current proof-of-concept study, archived plasma samples from 30 lung cancer patients were examined, along with 29 non-cancerous control samples matched by age, gender and smoking status. The study attempted to track the immediate upstream cause of aberrant glycans, namely the glycotransferase enzymes that build them—a process that takes place in the endoplasmic reticulum and Golgi apparatus of the cell.

“Most glycomics efforts look at intact glycans, but often this is not a good molecular surrogate for the activity of glycotranferases because glycotranferases work on hundreds of growing glycan polymers,” Borges notes. “Our new, bottom-up approach looks at glycans in a different way.” To evaluate glycotranferase activity, the study pooled together the glycan polymer branching points or nodes for all of the aberrant glycan structures observed. Specific sugar subunits and linkage types characterize these glycan nodes.

A technique known as gas chromatography/mass spectrometry was used to detect glycan node levels, which were then combined to infer glycotransferase activity. The study demonstrated that a number of glycan nodes exhibited a 1:1 molecular correspondence with particular glycotranferases. The technique was used to accurately pinpoint lung cancer in blood samples with 76-88 percent reliability.

While a number of hurdles must be addressed in future research, the new technique holds the promise of a simple test capable of analyzing multiple glycotransferases simultaneously and linking abnormal activity with the aberrant glycans formed by these enzymes. The test can be carried out without the need for enzyme or antibody reagents and provides a potential means of finally harnessing aberrant glycans as useful disease biomarkers.

The method’s effectiveness is expected to further improve once information from large data sets of known patient outcome are applied and analyzed. This will hopefully permit the development of disease-specific biomarkers for a range of ailments including cancers and other inflammation-related diseases.

Applying the glycan-node strategy directly to cancerous fluids or tissues, rather than plasma/serum (where normal glycans tend to dilute the desired signal) may further enhance the test’s sensitivity. “The interesting thing is that we see widely different glycan profiles for different biofluids and different tissues, suggesting that they will be able to provide information above and beyond what blood serum alone can provide,” Borges says.

The method, once refined, may offer clinicians an extra piece of evidence on which to base decisions concerning invasive procedures (like lung biopsy or pancreatectomy) for confirming cancer diagnosis and charting appropriate treatment.

Source: Multiplexed surrogate analysis of glycotransferase activity in whole biospecimens.

Source: Arizona State University Biodesign Institute

OGT Launches PGS Array to Improve the Chances of Successful IVF

Oxford Gene Technology (OGT), provider of innovative genetics research and biomarker solutions to advance molecular medicine, has announced the launch of a new pre-implantation genetic screening (PGS) array aimed at improving the chances of successful in-vitro fertilisation (IVF).

The array detects chromosome number abnormalities (aneuploidy) across all 24 human chromosomes using DNA amplified from a single cell from an early-stage embryo. This allows selection of an embryo with a normal chromosomal content.

The number of women receiving IVF has increased steadily, however the percentage of IVF treatments resulting in viable pregnancies is still comparatively low with chromosomal aneuploidy a leading genetic cause of unsuccessful IVF. It has been reported that 75% of eggs in women over 37 and 23% of eggs in younger women are chromosomally abnormal1.

OGT’s CytoSure™ Single Cell Aneuploidy array is the first commercially available oligonucleotide aCGH product designed specifically for PGS. The array is sensitive enough to work with small amounts of amplified DNA from a single cell from an early-stage embryo. Unlike technologies such as fluorescence in situ hybridisation (FISH), the array can detect aneuploidies across the whole genome. The array allows eight samples to be run simultaneously, which is more than existing bacterial artificial chromosome (BAC) aneuploidy arrays, minimising sample-to-sample variation by reducing technical noise.

The array is complemented by OGT’s CytoSure Interpret Software which analyses the data generated to produce simple, easy-to-use results. The ability to clearly identify aneuploidy is vital to make a confident and informed decision as to the chromosomal content of an embryo. The array has also been research-validated to investigate aneuploidies in first polar bodies, single blastomeres and trophectoderm biopsies.

Dr Mike Evans, CEO, OGT said, “With the launch of the CytoSure Single Cell Aneuploidy array we are moving into a new and valuable area both as a company and in the wider sense of seeking to improve reproductive health. The superior resolution, throughput and full chromosome coverage of our array allows improved identification of aneuploidy. We are hopeful that this new product will contribute significantly to helping potential parents maximise their chances of IVF success.”

Source: Oxford Gene Technology