2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-NGS assay for simultaneous screening of DNA and RNA provides a comprehensive solution guiding clinical management of ALL patients

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A comprehensive genomics profiling assay that simultaneously screens DNA and RNA for expression and variants has been developed for the clinical management of patients with acute lymphoblastic leukemia (ALL). Accurate molecular characterization of ALL subtypes is important for guiding therapeutic intervention. A key molecular indicator associated with poor prognosis in Ph-like ALL patients is the upregulation of CRLF2 expression, which can be caused by gene fusion or mutations. Most panel-based assays screen either DNA or RNA separately, leading to higher cost and longer processing time. However, this new assay uses a single tube and total nucleic acid as input, allowing for simultaneous screening of DNA and RNA. The assay provides a comprehensive genetic profile for diagnosis and therapeutic guidance in Ph-like ALL patients.<br /><br />The study identified several molecular findings in non-Ph ALL patients. The most commonly affected gene in Ph+ patients was IKZF1, while IKZF1 and JAK1/2 were frequently altered in Ph-like cases. The most common fusions identified in the non-Ph cases were KMT2A and RUNX1. In some cases, a fusion molecular driver could not be identified, prompting investigation into gene expression profiles. Differential gene expression analysis identified three genes (ELL, KANK1, and CDKN2A) that were significantly upregulated in cases with no molecular driver compared to the rest of the cohort. These genes have established links to hematological conditions or hereditary cancer and may provide insights into potential drivers in these cases.<br /><br />The assay demonstrates a powerful and cost-effective tool for comprehensive genomics profiling in ALL patients. It allows for the classification of ALL samples and provides guidance for therapeutic intervention based on the genetic profile. The study also ensured the uniformity of assay performance by testing CRLF2 expression across different sample types, genders, and clinical diagnoses in a pilot cohort. Overall, the NGS assay has the potential to enhance the clinical management of ALL patients by providing a comprehensive solution for molecular characterization and therapeutic guidance.

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Presenting Author - Lina Zelinger, PhD; Co-Author - Charmeine Ko, PhD; Co-Author - Francys Alarcon, B.Sc; Co-Author - Samuel Koo, M.Sc; Co-Author - Kenneth B. Thomas, PhD; Co-Author - Hyunjun Nam, PhD; Co-Author - Fernando J. Lopez Diaz, PhD; Co-Author - Segun C. Jung, PhD; Co-Author - Fei Ye, PhD; Co-Author - Shashikant Kulkarni, PhD, FACMG, MBA;

Meta Tag

Bioinformatics

Clinical Applications of Molecular Cytogenetics

NextGen Sequencing

Oncogenesis

Sequencing

Variant Detection

Co-Author Charmeine Ko, PhD

Co-Author Francys Alarcon, B.Sc

Co-Author Samuel Koo, M.Sc

Co-Author Kenneth B. Thomas, PhD

Co-Author Hyunjun Nam, PhD

Co-Author Fernando J. Lopez Diaz, PhD

Co-Author Segun C. Jung, PhD

Co-Author Fei Ye, PhD

Co-Author Shashikant Kulkarni, PhD, FACMG, MBA

Presenting Author Lina Zelinger, PhD

Keywords

genomics profiling assay

acute lymphoblastic leukemia

CRLF2 expression

gene fusion

mutations

comprehensive genetic profile

therapeutic guidance

IKZF1

JAK1/2

NGS assay