Breaking News
August 16, 2018 - Promoting HPV Vaccine Doesn’t Prompt Risky Sex by Teens: Study
August 16, 2018 - Treating Rheumatoid Arthritis: Search for a Cure
August 16, 2018 - Research shows in the long run, charcoal toothpaste likely won’t whiten teeth
August 16, 2018 - Seattle Children’s opens new clinic to provide convenient access to pediatric specialty care services
August 16, 2018 - Curious case of the lost contact lens
August 16, 2018 - GN Hearing unveils world’s first Premium-Plus hearing aid
August 16, 2018 - Parental life span linked with increased longevity and health in daughters
August 16, 2018 - Health leaders reveal ten most important medicines in NHS history
August 16, 2018 - Mobile health devices diagnose hidden heart condition in at-risk populations
August 16, 2018 - When it comes to shedding pounds, it pays to think big
August 16, 2018 - Liva Healthcare announces appointment of Thomas Cooke as clinical services manager in the UK
August 16, 2018 - New digital pharmacy aims to help people living with chronic care conditions
August 16, 2018 - Preventing ACL injuries in high school athletes
August 16, 2018 - Experts provide insight into novel concepts and approaches for stroke rehabilitation
August 16, 2018 - Scientists reverse congenital blindness in mouse model
August 16, 2018 - Study shows link between use of benzodiazepines and increased risk of Alzheimer’s disease
August 16, 2018 - Trial shows PARP inhibitor as novel treatment option for patients with advanced breast cancers
August 16, 2018 - Prenatal exposure to violence increases toddlers’ aggressive behavior to their mothers
August 16, 2018 - Can manipulating gut microbes improve cardiac function in patients with heart failure?
August 16, 2018 - Hearts of newborn piglets can completely heal after heart attacks
August 16, 2018 - Ablating the mutant p53 gene in mice with colorectal cancer inhibits tumor growth
August 16, 2018 - Higher BMI in people with prediabetes related to evening preference and lack of sufficient sleep
August 16, 2018 - Using peripheral nerve blocks to treat facial pain may produce long-term pain relief
August 16, 2018 - Neural stem cells are the key to tail regeneration
August 16, 2018 - Study compares genetic and neural contributions to ADHD in children with or without TBI
August 16, 2018 - Adding energy drinks to alcohol may exacerbate negative effects of binge drinking
August 16, 2018 - Eye Examination Can Help Detect Abuse in Children
August 16, 2018 - Know the Difference: Rheumatoid Arthritis or Osteoarthritis?
August 16, 2018 - From ‘sea of mutations,’ two possible cancer links rise to the surface
August 16, 2018 - Does medical school take too long?
August 16, 2018 - Brown University researchers reveal key physical properties of ‘giant’ cancer cells
August 16, 2018 - Regular resistance training improves exercise motivation
August 16, 2018 - Feds urge states to encourage cheaper plans off the exchanges
August 16, 2018 - Seven activities that prevent you from getting quality sleep during summer
August 16, 2018 - Five ways to tell if your baby is getting enough milk from breastfeeding
August 16, 2018 - From Pigs to Peacocks, What’s Up With Those ‘Emotional-Support Animals’?
August 16, 2018 - Breast cancers enlist the help of normal cells to help them spread and survive
August 16, 2018 - Engaging with “high-need” patients outside the clinic
August 16, 2018 - Research illuminates how online forum may offer suicide prevention support for males
August 16, 2018 - Researchers identify way to grow immune cells at large scale for preventing cancer reoccurrence
August 15, 2018 - Keck Medicine of USC’s hospitals ranked among nation’s best for the 10th consecutive year
August 15, 2018 - Researchers compare existing approaches for automating diagnostic procedures of skin lesions
August 15, 2018 - Autism risk determined by health of mom’s gut, research reveals
August 15, 2018 - WELL for Life challenges you to explore the great outdoors
August 15, 2018 - ‘Zombie’ gene protects elephants from cancer, study finds
August 15, 2018 - Ebola outbreak in Congo spreads to active combat zone
August 15, 2018 - Study highlights pollution exposure of babies in prams
August 15, 2018 - Study provides insight into link between sleep apnea and lipid metabolism
August 15, 2018 - New study focuses on promise of gene therapy for Amish nemaline myopathy
August 15, 2018 - Researchers discover new approach to alleviate chronic itch
August 15, 2018 - Uncovering the Mysteries of MS: Medical Imaging Helps NIH Researchers Understand the Tricky Disease
August 15, 2018 - Autistic people at greater risk of becoming homeless – new research
August 15, 2018 - New imaging technique can spot tuberculosis infection in an hour
August 15, 2018 - Scientists study effects of eating breakfast versus fasting overnight before exercise
August 15, 2018 - Talking with children about suicide could save lives
August 15, 2018 - Grip strength of children predicts future cardiometabolic health
August 15, 2018 - New polyclonal immunotherapy successfully neutralizes Ebola virus
August 15, 2018 - Innovative oncofertility program launched by RMA of New York and Mount Sinai Health System
August 15, 2018 - Study shows efficacy, safety of AAV5-based gene therapy to treat sheep model of achromatopsia
August 15, 2018 - Simple score helps predict which hospitalized heart attack patients are at high risk of readmissions
August 15, 2018 - New discoveries show how protein droplets do more than keep cells’ interiors tidy
August 15, 2018 - Study shows impact of optimizing airport flight patterns on human health
August 15, 2018 - Life experiences of feeling unwanted or unplanned associated with attachment insecurity
August 15, 2018 - ACS Briefing Discusses Use of Lessons From Combat Care
August 15, 2018 - Study identifies distinct origin of ADHD in children with history of brain injury
August 15, 2018 - IgG3 antibody stops B cells from fighting pathogens in HIV patients
August 15, 2018 - Scientists discover key vulnerability of mixed lineage leukemia
August 15, 2018 - College students may experience pressures from secondary exposure to opioid abuse
August 15, 2018 - Powerful new microscope reveals inner workings of human cells with unprecedented clarity
August 15, 2018 - Married people who fight nastily more likely to suffer from leaky guts, study suggests
August 15, 2018 - Working Out After Baby – Drugs.com MedNews
August 15, 2018 - Rheumatoid Factor (RF) Test: MedlinePlus Lab Test Information
August 15, 2018 - ADHD linked to an increased risk of injury in children, study finds
August 15, 2018 - UIC researchers receive NIH funding to develop a better way to regenerate bone or tissues
August 15, 2018 - Study reveals how immune cells in the brain influence sexual behavior
August 15, 2018 - Researchers move closer to finding potential soft spot in drug-resistant tuberculosis
August 15, 2018 - Real-time dynamic monitoring of cell’s nucleus for effective cancer screening
August 15, 2018 - Lower rates of Medicare preventive care visits found in racial, ethnic minority older adults
August 15, 2018 - Scientists identify stress hormone as key factor in failure of immune system to inhibit leukemia
August 15, 2018 - Cytoplan introduces three new nutritional supplements
Study finds false negatives in common tests used to determine ROS1 status in lung cancer

Study finds false negatives in common tests used to determine ROS1 status in lung cancer

image_pdfDownload PDFimage_print

Drugs like crizotinib are used to treat patients with ROS1-positive lung cancer. But which patients are ROS1-positive? A University of Colorado Cancer Center study published in the Journal of Thoracic Oncology shows that common laboratory tests used to determine ROS1 status all have inherent limitations that can lead to false-negative results. Some samples that were determined to be ROS1-negative by one test were shown to be ROS1-positive by another, meaning that some patients who could benefit from ROS1-directed therapy may be slipping through the cracks.

A commonly used test, based on a technique known as fluorescence in situ hybridization (FISH), provided a false negative for 2 of 20 samples known to be ROS1-positive; a test that sequences and analyzes ROS1 DNA was negative in 4 of 18 positive samples; and a test that looks for ROS1 fusion RNA was negative in 3 of 19 positive samples.

“The main point is just to be aware of the deficiencies in these assays and not to always trust a negative result from a single test. If you’re suspicious that a patient could be ROS1-positive – maybe they’re a never-smoker without other known drivers such as EGFR, ALK, KRAS, BRAF – then it may be useful to try another kind of test,” says Kurtis Davies, PhD, Lead Assay Development Scientist at the Colorado Molecular Correlates Laboratory (CMOCO).

Davies, the study’s first author, worked closely with colleagues including senior authors Robert C. Doebele, MD, PhD, director of the CU Cancer Center Thoracic Oncology Research Initiative, and Dara Aisner, MD, PhD, CMOCO Director in the CU Department of Pathology, which routinely employs multiple modes of testing cancer specimens.

“The University of Colorado has been a big player in the clinical research of ROS1 lung cancer, and so we have a lot more ROS1-positive samples than almost anywhere else. This allowed us to go back to our large bank of samples to test them in these three ways,” Davies says.

The study found that each test has inherent deficiencies. ROS1-positive cancers are caused by the gene ROS1 fusing with one of a number of partner genes. One of these possible partners sits very near to ROS1 on chromosome 6. When ROS1 fuses with this nearby partner, there may not be enough DNA deleted to identify the fusion using FISH.

“It can leave enough of the FISH probe binding sites that the sample appears normal even though a ROS1 fusion is present,” Davies says.

The deficiency in the DNA-based test was due to the inherent inability to properly sequence large areas of the ROS1 gene.

“You have large swaths of un-sequenced DNA and if the ROS1 change is in one of those areas, it’s possible to miss it,” Davies says.

“Some regions of DNA can be very challenging to sequence due to highly repetitive sequences, so simply trying to sequence those regions doesn’t necessarily fix the deficit,” Aisner says.

Unlike the other two tests, the assay based on RNA doesn’t attempt to take a snapshot of altered ROS1 DNA. Instead, it looks at what is manufactured from the DNA. This means that an RNA-based assay has the potential to more directly test for the results of ROS1 gene fusion that can drive cancer. That is, as long as you have good enough RNA.

“The deficiency in assays based on RNA is that they depend on RNA quality, which can be bad in clinical samples,” Davies says.

On the plus side, pathologists looking at the assay data can tell if RNA is of high enough quality to believe test results. (“We know when RNA quality is low,” Davies says.) In these cases, the FISH or DNA test could be used. And the false-negatives attributed to the RNA assay in this study were all due to low RNA quality.

“If you take out the negatives due to RNA quality (which we don’t really regard as negative), there were no false negatives with this kind of test,” Davies says.

Again, according to Davies, the takeaway is to realize there is no perfect test and sometimes secondary analysis with a different test is necessary to confirm results. The strategy is more than theory.

“We’ve run FISH concurrently with the RNA test for the past 18 months,” Davies says. “This helps us to provide every reassurance that we are not missing patients who can benefit from ROS1 directed therapy.”

The strategy of testing by two methods has paid off.

“One of the patients included in this study was initially determined to be ROS1-negative via FISH, but was subsequently shown to be ROS1-positive via RNA,” Aisner says. “This patient went on to receive ROS1 targeted therapy and demonstrated an impressive response.”

Tagged with:

About author

Related Articles