Next Generation Sequence-Based Targeted Somatic Mutation Analysis in Low and Intermediade-1 Risk Group Patients with Myelodysplastic Syndrome

Project no. 24188 · Status: Kapanmış · 2022

Summary

Next Generation Sequence-Based Targeted Somatic Mutation Analysis in Low and Intermediade-1 Risk Group Patients with Myelodysplastic Syndrome Objective: Prognostic assessment is of significant importance in myelodysplastic syndrome (MDS) due to the high variability in its clinical spectrum. Accurate prognostic estimation allows for the early identification of high-risk patients. Various prognostic scoring systems have been developed using parameters such as bone marrow blast percentage, the presence of cytopenia, and cytogenetic findings. However, it has been observed that even patients categorized as low-risk in these scoring systems exhibit high mortality and morbidity rates. Consequently, in recent years, molecular parameters have been used in addition to existing prognostic scoring systems and have been seen to be highly effective in prognostic prediction. This study aims to investigate the impact of molecular testing on the discrimination of low and intermediate-1 MDS patients, in addition to cytogenetic tests, in clinical practice.Materials and Methods: We included 21 bone marrow aspiration samples in our study. These samples belonged to patients whose low and intermediate-1 risk group with died patients with MDS. Also, these patients’ karyotype and FISH analysis results were normal. Next generation sequencing panel covering 58 genes was used in the somatic mutation analysis of the samples. The molecular data obtained, along with the patients' clinical data, were input into the IPSS-M risk scoring program, and the patients' new risk groups were determined.Results: The analysis detected a total of 222 mutations, which are Tier 1 or Tier 2, in 26 different genes in 20 out of 21 patients (95%). According to IPSS, seven of the included patients were classified as low risk, and 14 were categorized as intermediate-1 risk. Following molecular analysis, the detected mutations were input IPSS-M risk scoring program and new risk group was created. Amongst the examined patients, 16 patients (76%) have been reclassified to higher-risk groups. Only two patients exhibited transformation to acute myeloid leukemia (AML), with one patient being detected with the IDH2 R140Q mutation (AF: 43%) and the other having mutations in four different genes (RUNX1, ETV6, U2AF1 and DNMT3A) with allele fractions above 20%.Conclusion: The DNA concentrations extracted from bone marrow aspiration samples of all patients were sufficient for the study. As a result of molecular analyzes, 76% (16 patients) of the patients, which are low-risk MDS, in our study were reclassified as a higher risk group. This study underscores the necessity of incorporating molecular tests into routine clinical practice for low-risk MDS patients. Furthermore, our study aims to pave the way for future studies in our country.Keywords: Myelodysplastic Syndrome; Somatic Mutation Analysis; Next Generation Sequencing; IPSS-M

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