Jessica Wright¹, Tamaryn J Knezovitch¹, Mark G Williams¹, Ritesh Chatrapati², Pauline Higgins², Amanda Goh^2,3, Abhijit Kulkarni¹, Edward Chew¹

¹Genomic Diagnostics, 460 Lower Heidelberg Road, Heidelberg, Victoria, 3084; ²QML Pathology, 11 Riverview Place, Murarrie, Queensland, 4172; ³Faculty of Medicine, The University of Queensland, 20 Weightman St, Herston QLD 4006

The introduction of Medicare-funded Next Generation Sequencing (NGS) panel testing for haematological malignancies has transformed diagnostic workflows, offering unparalleled insights into the genetic basis of these disorders. The extensive data generated by NGS significantly increases the analytical workload which raises critical questions about the clinical utility of this additional information: does it genuinely assist clinicians, and does it translate into better patient outcomes? To explore these questions, we focused on one key gene from the expanded NGS panel: SF3B1.

In a subset of patients investigated for haematological malignancies, we observed that SF3B1 mutations frequently co-occurred with JAK2, CALR, and MPL driver variants. Through a series of case studies, we illustrate how the detection of SF3B1 mutations added significant diagnostic value, refining disease classification and informing clinical decision-making.

Our findings emphasize that while the complexity of NGS data can be challenging, its capacity to reveal the genetic heterogeneity of myeloproliferative neoplasms / myelodysplastic syndrome (MPN/MDS) markedly enhances diagnostic accuracy and patient care. We conclude that the investment in comprehensive NGS testing is not only justifiable but essential for delivering precise and impactful diagnoses.