Tag Archives: Pharmacogenetics)

January 2024—Sometimes even superb ideas can also turn out to be quite, well, bothersome. Zoom meetings. Bridal showers. Bike lanes. Parking apps. QR menu codes. And—if laboratories aren’t careful—the same can be true of pharmacogenomic testing. Just ask Ann Moyer, MD, PhD, associate professor, laboratory medicine and pathology, Mayo Clinic. When it comes to pharmacogenomic testing, laboratory medicine brings significant expertise to the table. But in clinical settings, physicians who prescribe the medications need to be familiar with how to use the test results. They also need to work with the lab to decide which tests, for which genes or gene-drug pairs, will be most helpful for their patients, she says. “Especially if you’re going to start incorporating clinical support alerts into the EHR,” adds Dr. Moyer, who was chair of (until Dec. 31; she is now advisor to) the CAP/ACMG Biochemical and Molecular Genetics Committee. “If the practice doesn’t actually want them, then you’re just going to end up annoying them.”

October 2023—Next-generation sequencing of tumor tissue has important implications in solid and hematologic malignancies because it can identify genomic variants that provide diagnostic, prognostic, and predictive information to guide clinical management. Variants identified on tumor sequencing can be classified as somatic (acquired after conception) or inherited through germline.

September 2023—What happens when an oncologist cannot confidently determine what type of genetic test to order for their patient? Where can a provider turn if they do not know whether a genetic variant is clinically actionable? As genetic testing becomes a more integral part of personalized medicine and health care in general, there is a growing need to bridge the gap between those skilled in molecular diagnostics and those on the patient-facing side of care. In response to this need, the Center for Integrated Diagnostics (CID), a high-complexity molecular diagnostics laboratory at Massachusetts General Hospital, created its Consultation Service.

July 2023—Bringing new technology into laboratories is important for pathology as a field and for patients—and only getting more difficult. “Each new wave of technology is more complicated than the last,” Jeremy Segal, MD, PhD, said at the USCAP meeting this spring.

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.

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.”

April 2023—After years of excitement and scientific breakthroughs, the use of molecular testing to guide cancer therapeutics finally is coming into its own. Unfortunately, it appears to have landed in the wrong place at the right time. That place is a lonely spot, surrounded by gaps in economics and coverage, as well as knowledge, guidelines, ordering patterns, turnaround times, reporting, and the like. So plentiful are the gaps that, put together, they could form a vast, inhospitable space, a veritable Colorado Plateau, with molecular testing as a majestic, enticing but remote rocky pinnacle in the middle. Think Monument Valley. It’s worth the trek. The evidence in support of genomic profiling continues to grow. Simply put, “Patients with the right markers who get the right drugs do better,” says Neal Lindeman, MD, vice chair, laboratory medicine and molecular pathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine/New York Presbyterian Hospital. But as numerous studies are showing, the lag in testing is growing as well.

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.

April 2022—Genetic alterations of the gene FLT3, especially internal tandem duplications in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are commonly seen in patients with newly diagnosed myeloid leukemias. However, chromosome rearrangements involving the FLT3 gene are extremely rare in hematologic malignancies. The FLT3 gene has only a few known partner genes, including the gene ETV6, which encodes a transcriptional repressor. ETV6 has a wide variety of translocation partner genes, several of which are tyrosine kinase genes.

January 2022—“Workflow” evokes a process that moves smoothly, like water, that doesn’t break down or grind to a halt, a sequence of steps that can be completed in a seamless manner. Genomic workflows in information systems, however, have an especially poor fit with the concept of “flow.” As genomic data migrate from the laboratory to an electronic health record or from one EHR to another, significant gaps can result between generation, interoperability, and utilization that may lead the data to miscommunicate or mislead. “The technology behind next-generation sequencing and genetic testing in general has advanced by leaps and bounds over the last 10 to 15 years,” says Alexis Carter, MD, physician informaticist, pathology and laboratory medicine, Children’s Healthcare of Atlanta. While the use of genomic testing has expanded rapidly, “information systems and electronic health records have really not been able to keep up.”

November 2021—At NorthShore University HealthSystem in suburban Chicago, a homegrown bioinformatics solution is the “secret sauce” that powers the health system’s personalized medicine program, says Kamalakar Gulukota, PhD, MBA, director of NorthShore’s Center for Bioinformatics and Computational Biology.

November 2021—Molecular analysis of advanced stage tumors has become the gold standard for identifying potential targetable mutations with high sensitivity, even in limited size tissue samples. However, when only tumor tissue is sequenced, it is difficult to differentiate between somatic mutations in the tumor cells versus constitutional (germline) mutations.

October 2021—Recent molecular genetic advances have dramatically expanded diagnostic options, thus revolutionizing the diagnosis of many tumor types, especially those of soft tissue and bone. Advances in the discovery of molecular alterations underlying neoplastic pathogenesis have also provided insights into novel therapeutic targets and prognostic biomarkers. These improvements have led to the reclassification of a growing list of previously established tumor types, resulting in significant challenges for practicing pathologists, as exemplified herein.

October 2021—Detecting leukemic cells for post-treatment monitoring in normal karyotype acute myeloid leukemia is challenging, but new approaches to minimal residual disease monitoring may make it increasingly possible in the clinical laboratory, David Wu, MD, PhD, said in an AMP webinar he presented recently on myeloid malignancy minimal residual disease detection.

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.

September 2021—The latest data on the use of two genomic assays in early-stage breast cancer and at the University of Rochester Medical Center as the pandemic set in were reported in a CAP TODAY webinar presented by William Audeh, MD, and David G. Hicks, MD. Dr. Audeh, medical oncologist and chief medical officer of Agendia, developer of MammaPrint and BluePrint, presented the long-term follow-up results of the MINDACT trial and an age-related analysis, as well as new data on MammaPrint’s use in endocrine therapy decisions.

May 2021—Most of the time, bloodstream infection antimicrobial resistance results achieved with blood culture molecular ID panels will be accurate. When and why they might not be was the focus of an AMP 2020 virtual session. “I don’t want to lead anyone to believe that these are not good, accurate, and important types of tests,” Richard E. Davis, PhD, D(ABMM), MLS(ASCP)CM, said of the panels.

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.

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.

October 2020—B-ALL with aberrant expression of myeloid markers should be investigated further for specific gene abnormalities, including ZNF384 rearrangements, and microarray analysis may play an important role.

October 2020—With MGMT gene promoter methylation observed in about 50 percent of glioblastomas, it remains a biomarker of strong clinical interest in routine practice, even though it’s not the sole determinant in decisions related to therapy. PCR and pyrosequencing are the most commonly used assays, and there’s a technique that is not yet mainstream but gaining interest, said Tejus A. Bale, MD, PhD, assistant attending pathologist in the Department of Neuropathology and Diagnostic Molecular Pathology, Memorial Sloan Kettering Cancer Center. Dr. Bale spoke June 30 in the first of a series of Association for Molecular Pathology webinars on emerging and evolving biomarkers.

September 2020—Genetic testing in ovarian cancer has a therapeutic implication that will aid in developing a treatment plan, and it is pathologists who should take the lead in creating the testing protocol, said Samuel Caughron, MD, pathologist, president, and CEO of MAWD Pathology Group, in a recent CAP TODAY webinar. Dr. Caughron explained the rationale for universal homologous recombination deficiency testing in patients with advanced ovarian cancer. The webinar, made possible by a medical sponsorship from AstraZeneca, is at <a href="https://www.captodayonline.com">www.captodayonline.com</a>.