Author: Kelly Grooms

New Cleared IVD Assay for Microsatellite Instability in Colorectal Cancer Aims to Help Identify Those with Lynch Syndrome

Posted on by Kelly Grooms

Lynch syndrome is an inherited condition that significantly increases the risk of developing colorectal and other cancers, often at a young age. People with this condition have close to an 80% chance of developing colorectal cancer in their lifetime. It is the most common form of hereditary colon cancer and causes roughly 3% of all colon cancers. The mutations that cause Lynch syndrome are inherited in an autosomal dominant manner— ­meaning you only need to have one copy of the gene with a Lynch-associated mutation to be at an increased risk.

It is estimated that 1 in every 279 people have inherited a Lynch-associated mutation (1). Yet despite this prevelence, Lynch syndrome is not well known and ~95% of those with the syndrome don’t know they have it (1).

Lynch Syndrome Cause and Detection

Lynch syndrome is caused by mutations that result in the loss of function of one of the four different major mismatch repair proteins. These proteins act as “proof readers” that correct errors in the DNA sequence that can occur during DNA replication. To determine if Lynch syndrome is likely, simple screening tests can be performed on tumor (cancer) tissue to indicate if more specific genetic testing should be considered. One such screening looks for high levels of microsatellite instability (MSI) in the tumor tissue. High microsatellite instability (MSI-H) in tumor tissue is a functional indication that one or more of the major mismatch repair proteins is not functioning properly.

Watch this short video to learn more about microsatellite instability.

For those who develop colorectal cancer at an early age or have a family history (immediate family member or multiple family members with colorectal cancer or polyps), screening for Lynch syndrome can offer valuable insight for both patients and their family, as well as for their healthcare provider.

New MSI IVD Test for Colorectal Cancer to Help Identify Lynch Syndrome

The newly released Promega OncoMate™ MSI Dx Analysis System is an FDA-cleared IVD Medical Device and can be used to determine the MSI status of colorectal cancer tumors to aid in identifying those who should be further tested for Lynch syndrome. The OncoMate™ MSI Dx Analysis System builds upon the company’s fifteen year history of supporting global cancer researchers with one of the leading standard tests for MSI status detection. The OncoMate™ MSI Dx Analysis System offers an improved formulation while using the same five markers that have become the gold standard for MSI detection in the research community and is referenced in over 140 peer review publications (2,3).

The OncoMate™ MSI Dx Analysis System is designed to provide physicians with a functional, molecular measurement of the level of DNA mismatch repair deficiency demonstrated within their patient’s colorectal cancer tumor. MSI testing is recommended to identify candidates for further diagnostic testing for Lynch syndrome. (2–4). The System is part of a broader workflow that includes DNA extraction from FFPE tissue samples, quantitation of DNA, amplification of specific microsatellite markers using multiplex PCR, fragment separation by capillary electrophoresis, and data analysis and interpretation software. The OncoMate™ MSI Dx Analysis System is available in certain countries.  Visit the OncoMate™ MSI Dx Analysis System webpage to learn more.

Promega previously announced a CE-marked version of the OncoMate™ MSI  Dx Analysis System in France, Germany, Austria, Poland, UK, Ireland, Belgium, Netherlands, Luxembourg, Spain, Italy, Switzerland, Denmark, Sweden and Norway.

For more information about MSI solutions available from Promega visit our Microsatellite Instability Testing webpage.

References

  1. Win, A. K. et al. (2017) Cancer Epidemiol. Prev. 26, 404–12.
  2. Bacher, J. et al. (2004) Dis. Markers 20, 237–50.
  3. Svrek, M. et al. (2019) Bull. Cancer, 106, 119–28.
  4. Umar, A. et al. (2004) J. Natl. Cancer Inst. 18, 261–8.

Questions Arise about TMB as a Predictive Biomarker for Immune Checkpoint Inhibitor Therapy

Posted on by Kelly Grooms
Artist rendition of immune cells attacking a cancer cells. Immune checkpoint inhbitor therapy is a relatively new therapy for certain cancers.

Immune checkpoint inhibitor (ICI), or immune checkpoint blockade, therapies are a revolutionary, and relatively new, approach to treating cancer. These therapies work by blocking immune checkpoint proteins that act to negatively regulate the immune system through the PD-1 pathway. Some tumors express immune checkpoints to prevent the immune system from producing a strong enough immune response to kill the cancer cells. When these checkpoint proteins are blocked by an ICI, the body’s T-cells can recognize and kill the cancer cells. ICI therapies show tremendous promise. Unfortunately, not all tumors express immune checkpoint proteins, and so, not all tumors will be effectively treated with ICI therapies. The challenge is differentiating between the tumors that will respond and tumors that won’t.

DNA Mismatch Repair Deficiency Status as Detected by Microsatellite Instability or Immunohisotchemistry are Important Biomarkers for ICI

Biomarkers are measurable indicators of a clinical condition that can be found in tissue, blood, or other fluids. Predictive biomarkers for ICIs can help determine if these therapies are a suitable choice for treatment. Some tumors have deficiencies in their DNA mismatch repair mechanisms. Mismatch repair deficiency (dMMR) leads to the accumulation of mutations across the genome, particularly in microsatellites, which over time can result in higher levels of neoantigen production, rendering the tumors susceptible to the ICI therapy (1–5).

In 2017, Le et al. demonstrated that dMMR status reliably predicted response to an ICI therapy targeting the PD-1 checkpoint protein (6). Following this discovery, ICI based on dMMR  determined using either microsatellite instbility (MSI) or immunohistochemistry (IHC), gained clearance from the US Food and Drug Administation (FDA) for microsatellite instability-high (MSI-H) or dMMR by IHC solid tumors. This was the first time a cancer treatment was cleared based on a biomarker regardless of cancer origin (1,7).  Since then, MSI-H and dMMR, have become some of the most recognized tissue agnostic biomarkers for improved survival following ICI therapy of solid tumors (6,8,9).

Continue reading “Questions Arise about TMB as a Predictive Biomarker for Immune Checkpoint Inhibitor Therapy”

Improving SARS-CoV-2 Antibody Detection with Bioluminescence

Posted on by Kelly Grooms
3D artistic rendering of the Lumit SARS-CoV-2 antibody test

Science is the practice of figuring out how things work and then using that knowledge to further our understanding or to create tools that can solve problems facing the world. Bioluminescent tools and assays are examples of science doing all these things. Bioluminescence is the light-yielding (luminescence) chemical reaction that is used by many lifeforms. When fireflies flicker in the twilight, they are using bioluminescence to flash on and off.  Chemically, bioluminescence happens when an enzyme called luciferase acts on a light-emitting compound, luciferin, in the presence of adenosine triphosphate (ATP), magnesium and oxygen.

For scientists, bioluminescence can serve as a tool to help them understand many cellular functions. Since few animal or plant cells produce their own light, there is little to no background signal (light) to be concerned about. This lack of background means that all light coming from the sample can be measured. In fact, bioluminescence is often a preferred tool for scientists because it does not require an external light source or special filters, which are required for fluorescence-based technologies.

Promega scientists have developed bioluminescent tools and assays to support leading edge scientific research for decades, beginning in 1990 with the Luciferase biosensor technology based on firefly luciferase. Luciferase is a wonderful tool for studying how enzymes work because its output (light) is so easy to measure: samples are placed into a special instrument called a luminometer, and the amount of light being produced (Relative Light Units) is recorded. Bioluminescence technology can be configured to measure a variety of cellular biology, ranging from cell health to enzyme activity down to the specific event of turning a gene on or off. The advent of new techniques for genetic manipulation, along with an enhanced understanding of bioluminescence and the discovery and engineering of better luciferases, enables science to use bioluminescence in even more unique ways.

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There’s a Vaccine for That—Could mRNA Vaccines be Used to Prevent Cancer Recurrence?

Posted on by Kelly Grooms

mRNA vaccines came roaring onto the public stage in 2020. In the United States and Europe, two of the vaccines that are being used against the SARS-CoV-2 virus are mRNA vaccines. The scientific community has been talking about the potential of this technology against infectious diseases as well as cancer for several years, but no one thought that the first mRNA vaccines would make such a huge, and public, debut.

One big benefit of mRNA vaccines is the speed at which they can be developed. mRNA vaccines use messenger RNA particles to teach our cells to make a bit of protein, which then triggers our body’s immune response, and it is relatively easy to synthesize large amounts of mRNA in a laboratory. As promising as this sounds for infectious diseases, the application of mRNA vaccines for oncology might be even more exciting.

Could mRNA vaccines be used for personalized cancer vaccines?
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Impact of COVID-19 Pandemic on Cancer Diagnosis—When Fewer Cases of Cancer is Not Good News

Posted on by Kelly Grooms

The year 2020 was a year filled with things we didn’t do. The global COVID-19 pandemic meant we didn’t gather with family and friends; we didn’t attend concerts or sporting events; we didn’t even go to work or school in the same way. We also didn’t go to the doctor, and as a result, many countries and organizations are reporting that there was an alarming drop in the number of new cancer cases (1–6). Unfortunately, while fewer diagnosis might sound like a good thing, there is no evidence that the actual rate of new cancer occurrence is declining (7).  

COVID-19 Restrictions Impact Cancer Screening and Diagnosis

The drop in cancer diagnosis happened after countries began to put into place new restrictions intended to slow the spread of the SARS-CoV-2 virus. These measures often included limiting or pausing many routine screenings and doctor visits, which also limited or paused opportunities to diagnosis cancer. The resulting decline in new cancer diagnosis was dramatic. In the United States, there was a 46.4% decline in the number of newly diagnosed cases of six of the most common cancer types (breast, colorectal, esophageal, gastric, lung and pancreatic) per week between March 1, 2020 and April 18, 2020 (1,2,8).

Continue reading “Impact of COVID-19 Pandemic on Cancer Diagnosis—When Fewer Cases of Cancer is Not Good News”

Your Brain on COVID-19: Neurotropic Properties of the SARS-CoV-2 Virus

Posted on by Kelly Grooms
Artist conception of coronavirus in the brain. Researchers are investigating the neurotropic effects of SARS-CoV-2

Viruses are both fascinating and terrifying. Stealthy, insidious and often deadly, they turn our own cells against us. Over the past year, we have all had a firsthand view of what a new and unknown virus can do. The SARS-CoV-2 virus has caused a global pandemic, and left scientists and medical professionals scrambling to unravel its mysteries and find ways to stop it.

COVID-19 is considered a respiratory disease, but we know that the SARS-CoV-2 virus can affect other systems in the body including the vascular and central nervous systems. In fact, some of the most noted symptoms of SARS-CoV-2 infection, headache, and the loss of the sense of taste and smell, are neurological— not respiratory— symptoms.

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UWCCC Small Molecule Screening Facility Validates the Lumit™ Dx SARS-CoV-2 Immunoassay for High-Throughput SARS-CoV-2 Antibody Screening

Posted on by Kelly Grooms

Three researchers from the University of Wisconsin and the Small Molecule Screening Facility (SMSF) at the University of Wisconsin Carbone Cancer Center (UWCCC) have expanded their collaboration in new directions because of COVID-19. Before the pandemic, Gene Ananiev, PhD, Facility Manager of the SMSF, Tim Bugni, PhD, a Professor in the School of Pharmacy, and David Andes, MD, Professor of Medicine and Medical Microbiology and Immunology and Head of the Division of Infection Disease, worked together on antibiotic compound discovery and development, now they have added Covid-19-related projects to that list.

“It was kind of an interesting aside…” said David Andes “To try to see a need, fill a need.”

The need they saw was for tools that are necessary around any pandemic or infectious disease outbreak: Ways to quickly diagnose and manage those who are infected and ways to study the epidemiology of the disease—the distribution pattern and frequency, causes and risk factors for infection within a population. Specifically, the three were interested in an antibody test that could be used not only to understand the proportion of the population that might have already been infected with SARS-CoV-2, but that also could be used to evaluate the response to different vaccine candidates. 

Continue reading “UWCCC Small Molecule Screening Facility Validates the Lumit™ Dx SARS-CoV-2 Immunoassay for High-Throughput SARS-CoV-2 Antibody Screening”

Increasing Testing Efficiency with Multiplexed Detection of SARS-CoV-2 and Influenza A and B

Posted on by Kelly Grooms

In the Northern hemisphere, the cold and flu season is about to start. Most years that means people schedule flu shots, dust off chicken soup recipes and stock up on tissues. If they start to feel sick, they stay home for a day or two, drink hot tea, eat warm soup and—for the most part— go on with their lives. 

This is not, however, most years. This year the world is battling a pandemic virus, SARS-CoV-2. Symptoms of COVID-19, the disease caused by this virus, mirror those of the flu and common cold, and that overlap in symptoms is going to make life more complicated. Most years, a mild cough or minor body aches wouldn’t even warrant a call to the doctor. This year these, and other undiagnosed cold- and flu-like symptoms, won’t be easily ignored. They could mean kids have to stay home from school, and adults have to self-quarantine from work, for up to 2 weeks. In years past people might have been comfortable treating their symptoms at home, this year people will want answers: Is it the flu? Or is it COVID-19?

Continue reading “Increasing Testing Efficiency with Multiplexed Detection of SARS-CoV-2 and Influenza A and B”

Lessons in History, Hope and Living with Lynch Syndrome from the “Daughter of Family G”

Posted on by Kelly Grooms

Lynch Syndrome is the autosomal dominant hereditary predisposition to develop colorectal cancer and certain other cancers. This simple, one sentence definition seems woefully inadequate considering the human toll this condition has inflicted on the families that have it in their genetic pedigree.

They Called it a Curse

To one family, perhaps the family when it comes to this condition, Lynch Syndrome has meant heartache and hope; grief and joy; death and life. Their story is told by Ami McKay in her book Daughter of Family G, and it is at once both a memoir of a Lynch Syndrome previvor (someone with a Lynch Syndrome genomic mutation who has not yet developed cancer) and a poignant and honest account of the family that helped science put name to a curse.

“The doctors called it cancer. I say it’s a curse. I wish I knew what we did to deserve it.”

Anna Haab from Daughter of Family G (1)

The scientific community first met “Family G” as the meticulously created family tree, filled with the stunted branches that mark early deaths by cancer. The pedigree was first published in 1913 in Archives of Internal Medicine (2). In the article, Dr. Alderd Warthin wrote: “A marked susceptibility to carcinoma exists in the case of certain family generations and family groups.” In 1925, an expanded pedigree of circles and squares was published in Dr. Warthin’s follow up study in the Journal of Cancer Research (3).  But each circle and square in that pedigree denotes a person. Each line represents their dreams together for the future, and Ms. McKay wants us to know their names: Johannes and Anna, Kathrina, Elmer, Tillie, Sarah Anne (Sally); and—most importantly—Pauline. Because without Pauline there would be no story.

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Promega Leverages Long-Time Experience in MSI Detection with European Launch of CE-Marked IVD Assay for Microsatellite Instability

Posted on by Kelly Grooms

The genetic abnormality called microsatellite instability, or MSI, has been linked to cancer since its discovery in 1993 (1). MSI is the accumulation of insertion or deletion errors at microsatellite repeat sequences in cancer cells and results from a functional deficiency within one or more major DNA mismatch repair proteins (dMMR).  This deficiency, and the resulting genetic instability, is closely related to the carcinogenicity of tumors (2).

Historically MSI has been used to screen for Lynch Syndrome, a dominant hereditary cancer propensity. More recently, tumors with deficient MMR function have been identified as being more likely to respond to immune checkpoint inhibitor (ICI) therapies (3.). Because MSI can be the first evidence of an MMR deficiency, MSI-High status is predictive of a positive response to immunotherapies such as ICI therapies. (3).

Learn more about MSI in this short animation.
Continue reading “Promega Leverages Long-Time Experience in MSI Detection with European Launch of CE-Marked IVD Assay for Microsatellite Instability”