Somatic Mutational Landscape in Patients with Primary Myelofibrosis

Activity: Talk or presentation types › Poster presentation

Description

Primary myelofibrosis (PMF) is the most aggressive subtype of the BCR-ABL-negative myeloproliferative neoplasms (MPN). Mutations in JAK2, CALR and MPL genes are defined as phenotype driver mutations and are included in WHO 2016 diagnostic criteria. Patients with PMF frequently have multiple additional oncogenic mutations. Routine molecular testing for MPN in Latvia is limited to JAK2 and CALR testing and is only done at Rīga Stradiņš University Scientific Laboratory of Molecular Genetics (RSU SLMG). The aim of this study was to introduce and approbate new genetical testing method at RSU SLMG and to study the clonal status of patients with PMF.. 18 individuals (12 females and 6 males) with suggestive PMF diagnosis were selected from internal database. Custom next generation sequencing (NGS) panel was created allowing to detect genetic variations in 41 genes important for diagnosis, personalized treatment or risk stratification in PMF and related disorders. Sequencing was performed on iSeq (Illumina, USA). Identified variant interpretation was done following ClinGen, CGC and VISS guidelines.. Median age of patients at sample acquisition was 61 (ranging 30-72) years. 14 patients had a common driver variant in JAK2 and CALR and one patient had a driver mutation in other gene (KRAS) likely confirming PMF diagnosis in 15 of 18 patients. In three patients, no somatic mutations were detected. 11 of 15 patients had additional oncogenic mutations where most frequently mutated were DNA methylation regulators (DNMT3A - four cases) and histone methylation regulators (ASXL1 and EZH2, 3 and 2 respectively).. We successfully introduced new genetical testing method, for simultaneous somatic mutation analysis in multiple genes, for RSU SLMG, that could further be used in scientific research and as a routine diagnostic testing for patients with MPN. We identified particularly large proportion of mutation-negative PMF samples, further clinical, laboratory and pathological reevaluation is needed.
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

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