October 2023—For molecular testing in oncology, the choice is often fast or slow. PCR-based platforms are rapid, and comprehensive genomic profiling by next-generation sequencing is slower, and each has its pros and cons.
Read More »In-house or send-out? Lab approaches to gene panels
May 2023—Achieving standardization and setting up processes around the use of next-generation sequencing panels for the care of patients with cancer is a long road requiring a lot of expertise.
Read More »The outlook for in-house next-generation sequencing
May 2023—Bringing next-generation sequencing in-house was at the center of a March 27 roundtable led by CAP TODAY publisher Bob McGonnagle, with costs, reimbursement, equity, and the electronic health record part of the conversation. Jeremy Segal, MD, PhD, of the University of Chicago, explains why the Genomics Organization for Academic Laboratories was formed. “By lowering barriers and encouraging cooperation,” he said, “we’ve seen our labs increase the pace of development and the quality of the assays they’re bringing on.”
Read More »No time to wait: How rapid NGS changed cancer care
November 2022—Rapid next-generation sequencing in a community hospital setting, performed by histotechnologists and interpreted by anatomic pathologists, is possible and paying off, and it “makes the pathologist a much more meaningful part of the precision oncology team,” says Brandon Sheffield, MD, of the Department of Laboratory Medicine, William Osler Health System, Brampton/Etobicoke, Ontario. “It has changed practice at our hospitals,” he says.
Read More »Checklists now made to fit for next-gen sequencing labs
October 2022—As the diagnostic uses for next-generation sequencing have grown, so too has the length of the NGS section of the CAP molecular pathology accreditation program checklist. Now, with the release of the new checklist edition this month, NGS laboratories will find the NGS section in their customized checklists leaner, more relevant, and easier to read.
Read More »Purchased for the pandemic? Rethinking instrumentation
October 2022—Who’s doing what with instruments purchased at the peak of the pandemic? That and next-generation sequencing are what CAP TODAY publisher Bob McGonnagle asked Compass Group members about when they met virtually on Sept. 6. The Compass Group is an organization of not-for-profit IDN system laboratory leaders who collaborate to identify and share best practices and strategies.
Integrating NGS into the cytopenia workup
May 2022—Myelodysplastic syndromes are often challenging to diagnose, and it’s the exceptions to the rules that make it so, said Phillipp W. Raess, MD, PhD, associate professor of pathology and laboratory medicine, Oregon Health and Science University, speaking at CAP21.
Read More »In next-gen sequencing, aiming for wider access
May 2022—Next-generation sequencing—the worries, the wins, and what’s new. That’s what came up when CAP TODAY publisher Bob McGonnagle led an NGS-focused roundtable on March 14. With him were Jeremy Segal, MD, PhD, of the University of Chicago; Pierre Del Moral, PhD, MBA, and Fiona Nohilly of Illumina; Sohaib Qureshi, PhD, of Thermo Fisher Scientific; and Andy Johnson, DPhil, of Janssen. Here’s what they had to say.
Read More »Metagenomic NGS: More pros than cons?
September 2021—A stem cell transplant patient at Lurie Children’s Hospital in Chicago had a disseminated fungal infection by every clinical criterion, but no conventional method had detected it.
Read More »A few years in, a new picture for liquid biopsy
July 2021—Liquid biopsy has entered a more confident era, with two FDA-approved next-generation sequencing assays for comprehensive tumor mutation profiling, evidence of its clinical utility, and broadened patient access.
Read More »Compass group roundtable: ‘Gaps loom large’: labor shortage hitting hard
June 2021—A brief update on SARS-CoV-2 variant testing and then a look at the latest on the laboratory labor struggle. That’s what Compass Group members provided when they spoke May 4 in another of their monthly calls led by CAP TODAY publisher Bob McGonnagle. “We’ve accepted that if we’re going to solve the [labor] issue,” said Sam Terese of Alverno Laboratories, “we’ll have to create the workforce. They’re not coming to us in any other way.” With McGonnagle and Terese were Bob Stallone and James Crawford, MD, PhD, Northwell; Sterling Bennett, MD, MS, Intermountain; John Waugh, MS, MT(ASCP), Henry Ford; Peter Dysert, MD, Baylor Scott & White; Steven Carroll, MD, PhD, Medical University of South Carolina; Stan Schofield, MaineHealth; Gregory Sossaman, MD, Ochsner; Clark Day, Indiana University; Diana Kremitske, MS, MHA, MT(ASCP), Geisinger; Julie Hess, AdventHealth; Terrence Dolan, MD, Regional Medical Laboratory; and Dan Ingemansen, Sanford. The Compass Group is an organization of not-for-profit IDN system lab leaders who collaborate to identify and share best practices and strategies. Here is what they said.
Read More »NGS in more labs? IFCC group aims to ease the way
May 2021—When it comes to next-generation sequencing, don’t count out community hospital labs, especially as black-box solutions come on the market. That’s the hope of members of an International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) working group that aims to help clinical labs develop in-house NGS programs. Large-scale genomic testing won’t be necessary or practical at the community hospital level. But hospital-based genomic testing programs should set out to meet the NCCN guideline targets and provide testing for which a wide range of sample input and quality can be accepted, says Robyn Sussman, PhD, a member of the IFCC working group and molecular development assistant director, Penn Precision and Computational Diagnostics, University of Pennsylvania Perelman School of Medicine.
Read More »Eyes on faster, cheaper, simpler next-gen sequencing
May 2021—Next-generation sequencing analysis and interpretation, as well as reimbursement, were some of what CAP TODAY publisher Bob McGonnagle asked Illumina and Thermo Fisher executives and Jeremy Segal, MD, PhD, about when they gathered on a March 24 call. McGonnagle asked, too, about variants of unknown significance and for views on what lies ahead for NGS. “Circulating tumor DNA analysis is starting to move wholesale into the academic setting,” along with other applications, says Dr. Segal, of the University of Chicago.
Read More »Seeking stability in gene nomenclature
April 2021—Human first names are not necessarily known for being meaningful—or unique for that matter. When Shakespeare’s Juliet muses, “What’s in a name?” she’s observing that her lover’s name is more or less an arbitrary label without relevance to the essence of Romeo.
Read More »Looming unknowns with SARS-CoV-2 variants
March 2021—Listening to experts and others make predictions about the pandemic, it’s easy to think they’re obsessed with surfing: How will we deal with the next wave? The dangers are real. With SARS-CoV-2, the next wave might be swept in by emerging variants, with their uncertain but worrisome impact on transmission, severity of illness, treatments, and vaccine effectiveness.
Read More »Markers, methods remake the NSCLC map
February 2021—Absorbing new biomarkers into lung cancer workups makes for a complicated diplomacy. How best to balance so many rivals? Does it make the most sense for laboratories to try to do everything at once, a full-court press involving next-generation sequencing panels? Or is it more practical to add a new marker only as a new targeted therapy receives approval? Where do RNA-based assays fit in? What about IHC? When do you make the switch? Or do you? And how best to handle cell-free DNA tests (which seem to be the rogue states in all this)? How do you weight external factors, such as reimbursement, existing equipment and capital expenditures, and physician expertise? Driving this all are medical breakthroughs. As with all forms of statecraft, the latest incident can change everything. For lung cancer, the most recent advance comes from the ADAURA trial, which showed a significant benefit of using osimertinib to treat stage IB to IIIA EGFR-mutation positive non-small-cell lung cancer.
Read More »AMP case report: NGS as the tiebreaker in tumors with similar morphology and equivocal immunophenotype
May 2020—Traditionally, histopathologic diagnosis has been regarded as the gold standard for most disease processes including cancer. However, in certain circumstances, a final histopathologic diagnosis cannot be rendered despite extensive conventional ancillary testing such as immunohistochemistry. In recent years, molecular testing has revealed specific variant signatures for many tumors, which can be used to determine a final diagnosis.
Read More »Mate pair sequencing yields rich new data
November 2019—The LUVOIR telescope proposed this year by NASA, when it is launched into orbit, will outperform the Hubble Telescope 40-fold in ability to detect and visualize deep space objects in detail. But while dazzling in concept, the LUVOIR is still in development. Interestingly, at the genomic level, a similarly impressive advance in detection called mate pair sequencing has already progressed from research to clinical use in diagnosing cancer. With mate pair sequencing, a novel next-generation sequencing technique, Mayo Clinic is advancing the laboratory’s current capabilities for visualizing genetic rearrangements, thus increasing the diagnostic yield of testing for a variety of neoplasms.
Read More »AMP case report: NGS of a rare metastatic bladder adenocarcinoma
September 2019—Primary bladder adenocarcinoma is a rare vesicle malignancy accounting for up to two percent of malignant neoplasms of the bladder.1 They occur in males more than females and are classically seen in the fifth or sixth decade of life.2 Histologically they are of enteric, mucinous, or mixed types. Morphologically, the enteric type appears identical to a colonic adenocarcinoma and the mucinous type appears as neoplastic cells floating in pools of extravasated mucin. The mixed type is a mixture of the morphologies of the enteric and mucinous types. Immunohistochemically, adenocarcinomas of the urinary bladder classically express CK20 and CDX2.
Read More »What UCLA learned in seven years of exome sequencing
May 2019—Never go it alone without the input of the ordering clinician, and the diagnostic yield is better than expected. Those are two of the five lessons UCLA learned in its first seven years of clinical whole exome sequencing.
Read More »In next-gen sequencing, ‘a lot more room to grow’
May 2019—Workflow, data interpretation, communication, and community—that and more came up when CAP TODAY publisher Bob McGonnagle spoke with five NGS experts in April: Boaz Kurtis, MD; Zhiyv (Neal) Niu, PhD; David Eberhard, MD, PhD; Luca Quagliata, PhD; and Arnaud Papin, MSc, MBA. What they said follows.
Read More »Can NGS replace routine respiratory testing? Study says not yet
March 2019—A small study performed at the University of Utah found that a next-generation sequencing assay cannot replace routine standard-of-care testing to detect pneumonia in immunocompromised patients and determine their treatment. But it could be ordered when an infection is suspected and all other testing has failed to find the etiology.
Read More »Drug-susceptibility testing for TB: poised to take a turn?
January 2019—In a large international study, whole genome sequencing with next-generation sequencing technology has proved its ability to accurately assess susceptibility of Mycobacterium tuberculosis isolates to four first-line drugs.
Read More »AMP case report: Detection of concurrent hematologic malignancies in solid tumor NGS testing may cause false-positive results
November 2018—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Weill Cornell Medicine.
Read More »With CMS coverage policy, NGS cancer testing goes large
July 2018—The March 16 announcement of a new Centers for Medicare and Medicaid Services coverage policy for next-generation-sequencing–based diagnostic lab tests for patients with advanced cancer did not appear out of the blue, since a draft policy was issued last fall.
Read More »NGS to take top spot as cancer biomarker testing broadens
June 2018—For biomarker testing and tissue conservation, all roads lead to next-generation sequencing, says Boaz Kurtis, MD, laboratory and medical director of Cancer Genetics in Los Angeles. Dr. Kurtis said, “There’s no other technology platform out there that can provide the amount of data we need today or will need in the future.”
Read More »Questions about frozen tissue, preanalytic variables, tumor content
June 2018—Boaz Kurtis, MD, laboratory and medical director of Cancer Genetics in Los Angeles, took the following questions from attendees at a webinar on NGS in routine non-small cell lung cancer biomarker testing.
Read More »Targeted NGS or exome? Consider the clinical context
December 2017—American writer Maile Meloy published a short story collection in 2009 titled Both Ways Is the Only Way I Want It. Molecular pathology laboratory directors faced with the variety of next-generation sequencing diagnostic panels might feel similarly. As the main character in Meloy’s title story asks, “What kind of fool wanted it only one way?”
Read More »NGS checklist takes in infectious disease testing
October 2017—The CAP issued its first accreditation checklist for next-generation sequencing in 2014, as NGS was becoming a tool used in a growing number of clinical laboratories. The list of requirements, which was a new section in the molecular pathology checklist, focused on constitutive (germline) testing and oncology testing.
Read More »In cancer sequencing, a new lingua franca
February 2017—NGS has taken its NBS, or next big step: a newly published joint consensus guideline on how to interpret and report sequence variants in cancer. With these 20 pages of best practices for making next-generation sequencing a regular part of cancer diagnostics, the field is moving, essentially, from frontier town to gated community.
Read More »Method or test? Providing clarity to clinicians on NGS
September 2016—Whether it was “This is your brain on drugs,” “Take a bite out of crime,” or “Friends don’t let friends drive drunk” popping up onscreen, few of us watching TV in the 1970s and ’80s enjoyed having our programs interrupted by those public service announcements. Yet those important messages stuck in viewers’ brains—and stuck hard, if homages such as the Washington Post’s “10 Best PSAs of All Time” are anything to go by.
Read More »Shorts on Standards: Update on the frontier of NGS, 7/16
July 2016—Next-generation sequencing has continued to deliver on its promises and potential in the diagnostic arena. However, as with any emerging and evolving technology, the medical and scientific community faces the challenge of assessing the implications and demonstrating definitive clinical uses of its expanding capabilities, especially in the context of medical efficacy, clinical utility, and cost efficiency.
Read More »Mosaicism adds to challenge in molecular diagnostics
May 2016—Newer gene sequencing methods based on massively parallel technology have enabled much deeper penetration into DNA composition, revealing nucleotide base alterations with a sensitivity never before attainable. While next-generation sequencing has yielded substantial clinical benefits, NGS results need to be interpreted carefully.
Read More »Next-gen sequencing workflow in full spate
April 2016—With next-generation sequencing’s clear benefits—for diagnosis, prognosis, treatment, and trials—come its new challenges, and clinical laboratories are doing what it takes and sharing how. Two plenary speakers at last year’s meeting of the Association for Molecular Pathology spoke of variant calling in the bioinformatic pipeline and validation, and of clinical reporting. Colin Pritchard, MD, PhD, of the University of Washington and one of the speakers, sees reporting a genomic sequencing assay as more like making a histologic diagnosis, which he calls craftwork, than reporting a sodium value. “That’s an idea that hasn’t really permeated yet,” he said.
Read More »In next-gen sequencing, panel versus exome
January 2016—As next-generation sequencing takes its place in clinical laboratory medicine, a difference is developing between its use when there is a defined phenotype, as with hereditary oncology syndromes or hereditary cardiovascular disorders, and its use in diagnosing hereditary developmental disorders. In oncology, targeted panels remain the optimal mode of application.
Read More »3 new NGS Surveys on CAP 2016 PT launchpad
November 2015—More than two years ago, when the CAP decided to move forward with proficiency testing for next-generation sequencing, the decision point was modest. “We estimated that about 35 labs would subscribe, based on survey information, and that was sufficient for us to move forward,” says Karl V. Voelkerding, MD, chair of the CAP Next-Generation Sequencing project team.
Read More »Next-gen sequencing settling in, making its mark
November 2015—Resource heavy, reimbursement challenged. Next-generation sequencing has its difficulties, but its value to patient care is without question. For many laboratories today, it’s a test sent out, but as for so many other tests, it won’t always be.
Read More »What’s new in next-gen sequencing checklist requirements
August 2015—The first CAP accreditation checklist requirements specific to next-generation sequencing were published only three years ago. “In 2012, those 18 accreditation requirements were basically all new language that the College’s Next-Generation Sequencing Project Team developed and submitted for review,” says project team chair Karl Voelkerding, MD, of the University of Utah Department of Pathology and ARUP Laboratories.
Read More »Paths to validating next-gen sequencing assays
July 2015—As more clinical laboratories tread the unfamiliar ground of next-generation sequencing, they are faced with the age-old challenges of establishing validation and quality control processes. Two experts tackled the topic of molecular QC during a recent CAP TODAY webinar presented in cooperation with Horizon Diagnostics and available for viewing on demand ...
Read More »For viral diagnosis, metagenomic NGS
June 2015—A 20-year-old woman who had returned to the U.S. after two months of hiking in Western Australia presented with three days of acute febrile illness—fever, rash, headache, nausea, and muscle and joint pain. Testing for common infectious causes of acute febrile illness, including Epstein-Barr virus, cytomegalovirus, and human immunodeficiency virus, all turned up negative. While the woman was in Australia, she had been warned about an ongoing outbreak of an exotic alphavirus, Ross River virus, in the region where she was hiking.
Read More »Groups closing the gap in reference materials for sequencing assays
March 2015—It’s a truism in the clinical laboratory that your results are only as good as the reference standards available to QC your assay. For measuring small analytes like glucose that’s not a problem. However, in clinical laboratories the analyte in question increasingly is DNA. In the past five years, next-generation sequencing has been adopted to detect variants in small targeted regions of specific genes, which is useful in oncology and medical genetics. More ambitious applications of NGS—whole genome and whole exome sequencing—have recently begun to enter the clinical realm as well.
Read More »NGS informatics catching up to clinical demands
November 2014—When Birgit H. Funke, PhD, gave a talk earlier this year on incorporating bioinformatic tools and pipelines into medical NGS, at Molecular Medicine Tri-Con 2014, one of her slides showed the main bioinformatics activities needed to support sequencing. Among them were designing and building pipelines to manage genetic data, writing scripts for data analysis pipelines, and building custom applications.
Read More »Virus or bacterium? Gene expression may tell
September 2014—At the 30th Annual Clinical Virology Symposium this spring, Gregory Storch, MD, related a typical case of a febrile child seen in the emergency department. Dr. Storch, a professor of pediatrics at Washington University School of Medicine, described a 20-month-old boy with a fever of 40°C, rash, cough, and nasal congestion but no gastrointestinal symptoms. White blood cell count was 7,800/µL. Blood culture was negative and a chest x-ray showed mild peribranchial thickening. Diagnosis, Dr. Storch says, was “viral syndrome.” The patient got a dose of ceftriaxone, which was “reasonable,” in Dr. Storch’s view, in light of the patient’s fever and the presence of bands on the peripheral blood smear.
Read More »NGS to detect oncogenes—sizing panels, reporting results
June 2014—Scientific wonders always abound at the Advances in Genome Biology and Technology conference, and this year’s meeting in February was no exception. Attendees had their first opportunity at a scientific meeting to learn about the newly announced Illumina HiSeq X Ten, a combination of 10 HiSeq X systems, which, Illumina says, can sequence 16 whole human genomes per three-day run at a read depth of 30× and a cost of $1,000 per genome. At the other end of the scale, attendees saw the unveiling of Oxford Nanopore’s MinION, a sequencer the size of a pack of chewing gum.
Read More »In encephalitis case, next-gen sequencing is the star
April 2014—In what may be a first for the burgeoning field of next-generation sequencing, this powerful new technology was used to identify the cause of encephalitis in a teenage boy who had been critically ill in the intensive care unit for several weeks. Diagnosis suggested a specific treatment. Within two weeks of initiating therapy, the boy had recovered and was discharged. It is becoming common practice to use NGS to detect mutations that can help select drug therapy in cancer cases and to find genetic variations responsible for inherited diseases. However, NGS has not previously been considered a useful tool in critical care situations, where a short turnaround time is crucial.
Read More »Next-gen sequencing now: a restless wave
November 2013—When it comes to home improvement projects, we all have our own comfort level. Some of us order a load of lumber and build a new addition to our home; others limit themselves to assembling a bookcase from Ikea. And there are those who leave everything to professionals.
Read More »For prenatal NGS labs, new accreditation requirements
September 2013—With the 2013 edition of the Laboratory Accreditation Program checklist, the College moves to a new level in its effort to ensure the highest-quality practices in clinical laboratories’ use of next-generation DNA sequencing.
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