Genomics and Molecular Pathology
Programme sponsor
Unified metagenomic method for rapid detection of microorganisms in clinical samples
Unified metagenomic method for rapid detection of microorganisms in clinical samples
Genomics and Molecular Pathology
Learning outcomes
This presentation will cover:
- Human DNA depletion for increasing sensitivity and reducing the TAT
- Detection of RNA and DNA microorganisms
- One sample, one test for detection of any type of microorganisms
Speakers
Dr Adela Alcolea-Medina
Optimising FLT3-ITD NGS for measurable residual disease detection in AML
Optimising FLT3-ITD NGS for measurable residual disease detection in AML
Genomics and Molecular Pathology
Abstract
FLT3-ITD (Fms-like tyrosine kinase 3 internal tandem duplication) mutations are prevalent in acute myeloid leukaemia (AML) and are associated with poor prognosis. As a marker of measurable residual disease (MRD), FLT3-ITD presents both opportunities and challenges depending on the detection method and clinical context. Here we aim to discuss the strengths and limitations of fragment analysis and next-generation sequencing (NGS) in FLT3-ITD detection, highlight method selection for MRD monitoring stages, and addresses key limitations in its clinical use.
Fragment analysis (capillary electrophoresis) remains a widely used technique due to its accessibility, speed, and ability to quantify ITD allelic burden. However, it has limited sensitivity (~1–5%) and may fail to detect low-level MRD. Additionally, it struggles with complex or longer insertions, particularly when polyclonal FLT3-ITD variants exist. In contrast, NGS offers significantly improved sensitivity (as low as 0.001%), can detect low-frequency clones, and provides detailed sequence-level information, enabling better resolution of polyclonal architecture and clone evolution over time.
For initial diagnosis and early post-treatment assessments, fragment analysis is often sufficient. However, for longitudinal MRD monitoring, particularly in patients with low disease burden or approaching transplant, NGS is the preferred method due to its superior sensitivity and specificity. Despite its utility, FLT3-ITD has inherent limitations as an MRD marker. These include instability of the mutation during treatment, potential loss or emergence of ITD clones, and difficulties in standardising NGS-based MRD thresholds. Furthermore, FLT3-ITD may not be the founding clone, limiting its reliability as a sole MRD target in some cases.
In conclusion, selecting the appropriate detection method and understanding the biological variability of FLT3-ITD are essential for accurate MRD monitoring. Integration of NGS into MRD workflows enhances detection but must be interpreted within the broader context of clonal evolution and other genetic markers.
Learning outcomes
Delegates who attend this presentation will:
- Evaluate Detection Methods: Understand the strengths and limitations of fragment analysis versus NGS for FLT3-ITD detection.
- Method Selection: Determine the appropriate FLT3-ITD detection method for each MRD monitoring stage.
- Recognize Limitations: Identify challenges and limitations in MRD monitoring using FLT3-ITD as a marker.
Speakers
Dr Nicola Potter
Homologous recombination deficiency (HRD) – Significance and clinical implications
Homologous recombination deficiency (HRD) – Significance and clinical implications
Genomics and Molecular Pathology
Abstract
Homologous recombination deficiency (HRD) has emerged as a critical biomarker in oncology, reflecting defects in the DNA repair pathway that contribute to genomic instability, cancer development, and treatment response.
HRD is particularly significant in cancers such as ovarian, breast, prostate, and pancreatic, where targeted therapies, such as PARP inhibitors, have shown clinical benefit. In practice, several methodologies and technologies are available to assess HRD status, with varying sensitivity and specificity. The National Genomic Test Directory (NGTD) mandates HRD testing across all Genomic Laboratory Hubs in England. At the South East GLH, we undertook an extensive validation process for a newly implemented, comprehensive next generation sequencing (NGS) panel. Comparative analysis with orthogonal assays and whole genome sequencing demonstrated acceptable concordance levels, supporting its clinical adoption. Crucially, assessment of HRD status beyond BRCA1/2 mutations is now pivotal for prescribing PARP inhibitors in ovarian and prostate cancers within England.
The talk will also address mechanisms of resistance to PARP inhibitors, an emerging challenge in clinical practice, and discuss how advancements in HRD testing may refine patient selection and guide future treatment strategies.
Learning outcomes
Delegates attending this presentation will:
- Understand the concept of HRD and its biological significance.
- Explore current techniques and technologies used to detect HRD.
- Assess the role of HRD testing in guiding treatment decisions and patient care.
- Consider emerging trends and advancements in HRD testing for future implementation.
Speakers
Dr Katya Mokretar PhD, DipRCPath, FIBMS
Exciting developments in spinal muscular atrophy (SMA): From testing to therapeutic treatment
Opening and Closing Plenary programmes
