A framework for the clinical implementation of optical genome mapping in hematologic malignancies

American Journal of Hematology, Journal Year: 2024, Volume and Issue: 99(4), P. 642 - 661

Published: Jan. 2, 2024

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches diagnostic scope of conventional standard care testing but it also adds significant new information in certain cases. Since consolidates benefits costly laborious tests (e.g., karyotyping, fluorescence situ hybridization, chromosomal microarrays) a single cost-effective assay, many laboratories started to consider utilizing OGM. 2021, international working group early adopters who are experienced with routine patients hematological neoplasms formed consortium (International Consortium Hematologic Malignancies, henceforth "the Consortium") create consensus framework implementation setting. The focus provide guidance implementing three specific areas: validation, quality control analysis interpretation variants. complex variables, we felt by consolidating our collective experience, could practical useful tool uniform hematologic malignancies ultimate goal achieving globally accepted standards.

Language: Английский

---

Optical Genome Mapping as a Diagnostic Tool in Pediatric Acute Myeloid Leukemia

Cancers, Journal Year: 2022, Volume and Issue: 14(9), P. 2058 - 2058

Published: April 19, 2022

Pediatric AML is characterized by numerous genetic aberrations (chromosomal translocations, deletions, insertions) impacting its classification for risk of treatment failure. Aberrations are described classical cytogenetic procedures (karyotyping, FISH), which harbor limitations (low resolution, need cell cultivation, cost-intensiveness, experienced staff required). Optical Genome Mapping (OGM) an emerging chip-based DNA technique combining high resolution (~500 bp) with a relatively short turnaround time. Twenty-four pediatric patients AML, bi-lineage leukemia, and mixed-phenotype acute leukemia were analyzed OGM, the results compared cytogenetics. Results discrepant in 17/24 (70%) cases, including 32 previously unknown alterations called OGM only. One newly detected deletion two translocations validated primer walking, breakpoint-spanning PCR, sequencing. As added benefit, identified new minimal residual disease (MRD) marker. Comparing impact on stratification de novo 19/20 (95%) cases had concordant while only unraveled another high-risk aberration. Thus, considerably expands methodological spectrum to optimize diagnosis via identification aberrations. will contribute better understanding leukemogenesis AML. In addition, may provide markers MRD monitoring.

Language: Английский

---

Advances in Molecular Understanding of Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis: Towards Precision Medicine

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1679 - 1679

Published: April 26, 2024

Myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), are characterized by the clonal proliferation of hematopoietic stem cells leading to an overproduction cells. The last two decades have seen significant advances in our understanding molecular pathogenesis these diseases, with discovery key mutations JAK2, CALR, MPL genes being pivotal. This review provides a comprehensive update on landscape PV, ET, PMF, highlighting diagnostic, prognostic, therapeutic implications genetic findings. We delve into challenges diagnosing treating patients prognostic mutations, evolution, impact emerging technologies like next-generation sequencing single-cell genomics field. future MPN management lies leveraging insights develop personalized treatment strategies, aiming for precision medicine that optimizes outcomes patients. article synthesizes current knowledge diagnostics MPNs, underscoring critical role profiling enhancing patient care pointing towards research directions promise further refine approach complex disorders.

Language: Английский

---

Analysis of comprehensive genomic profiling of solid tumors with a novel assay for broad analysis in clinical diagnostics

Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Somatic multigene analysis by next-generation sequencing (NGS) is routinely integrated in medical oncology for clinical decision-making. However, with the fast-growing number of recommended and required genes as well pan-cancer biomarkers, small panels have become vastly insufficient. Comprehensive genomic profiling (CGP) is, thus, to screen clinically relevant markers. In this multicentric study, we report on an extensive across seven centers comparing results novel OncoDEEP CGP assay diagnostically validated TruSight Oncology 500 (TSO500) kit 250 samples. Overall concordance was 90% gene variants >96% more complex biomarkers. Agreement fusion detection 94% 11 overlapping actionable driver genes. The higher coverage uniformity compared TSO500 allows users pool samples per run. Tertiary data analysis, including reporting, solution, whereas add-on TSO500. Finally, showed that, analytically, panel performs well, thereby advocating its use solid tumors diagnostic laboratories, providing all-in-one solution optimal patient management.

Language: Английский

---

Optical Genome Mapping: A Machine-Based Platform in Cytogenomics

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 113 - 124

Published: Jan. 1, 2024

Language: Английский

---

Real-World Clinical Utility of Targeted RNA Sequencing in Leukemia Diagnosis and Management

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2467 - 2467

Published: July 5, 2024

Gene fusions are key drivers in acute leukemia, impacting diagnosis and treatment decisions. We analyzed 264 leukemia patients using targeted RNA sequencing with conventional karyotyping reverse transcription polymerase chain reaction (RT-PCR). Leukemic were detected 127 (48.1%). The new guidelines introduced additional diagnostic criteria, expanding the spectrum of gene fusions. discovered three novel (RUNX1::DOPEY2, RUNX1::MACROD2, ZCCHC7::LRP1B). recurrent breakpoints for KMT2A NUP98 rearrangements. Targeted showed consistent results RT-PCR all tested samples. However, when compared to karyotyping, we observed an 83.3% concordance rate, 29 cases found only sequencing, 7 discordant results, 5 karyotyping. For five where known leukemic rearrangements suspected conducted messenger four proved no pathogenic advantageous rapid accurate interpretation concurrent use multiple methods was essential a comprehensive evaluation. Comprehensive molecular analysis enhances our understanding leukemia’s genetic basis, aiding classification. Advanced techniques improve clinical decision-making, offering potential benefits.

Language: Английский

---

Detection of Genomic Structural Variations Associated with Drug Sensitivity and Resistance in Acute Leukemia

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 418 - 418

Published: Jan. 18, 2024

Acute leukemia is a particularly problematic collection of hematological cancers, and, while somewhat rare, the survival rate patients typically abysmal without bone marrow transplantation. Furthermore, traditional chemotherapies used as standard-of-care for cause significant side effects. Understanding evolution to identify novel targets therefore, drug treatment regimens medical need. Genomic rearrangements and other structural variations (SVs) have long been known be causative pathogenic in multiple types cancer, including leukemia. These SVs may involved cancer initiation, progression, clonal evolution, resistance, better understanding from individual help guide therapeutic options. Here, we show utilization optical genome mapping (OGM) detect samples with Importantly, this technology provides an unprecedented level granularity quantitation unavailable current techniques allows unbiased detection SVs, which relevant disease pathogenesis and/or resistance. Coupled chemosensitivities these FDA-approved oncology drugs, how impartial integrative analysis diverse datasets can associate detected genomic sensitivity profiles. Indeed, insertion gene MUSK shown associated increased clinically agent Idarubicin, partial tandem duplication events KMT2A are related efficacy another frontline treatment, Cytarabine.

Language: Английский

---

Molecular pathology as basis for timely cancer diagnosis and therapy

Virchows Archiv, Journal Year: 2023, Volume and Issue: 484(2), P. 155 - 168

Published: Nov. 28, 2023

Language: Английский

---