Next-Generation Sequencing Gene-Panels for the Detection of Somatic Mutations in Patients with Myelodysplastic Syndromes and Congenital Preleukemic Disorders

Recent investigations suggested that marrow somatic changes can idntify malignant clones in children and young adults, with inherited bone marrow failure (IBMF) and with genetic predisposition to myelodysplastic syndrome (MDS). Detection of somatic mutations can help verify the diagnosis of MDS, and determine the risk of transformation to AML. Those changes are dynamic and close follow-up ensures stem cell transplantation prior to development of AML.

We aimed to improve our ability to detect somatic mutations by using a NGS-panel of about 50 genes known to be involved in leukemogenesis.

Overall, 44 pediatric and young adult patients were included, of which 21 (47.7%) presented with persistent cytopenia or MDS, and 23 (52.3%) had congenital preleukemic syndrome. We detected somatic mutations in 17 patients (38.6%). In patients with severe congenital neutropenia, we detected mutations in CSF3R and RUNX1; in two patients with Fanconi anemia mutations in SF3B1 and PPM1D were found. One patient with Schwachman Diamond syndrome had a mutation in FLT3. In addition, in 2 out of 3 patients with germline mutation in SAMD9L, additional somatic mutations in the same gene were found. For the patients with prolonged cytopenias and MDS, somatic mutations appeared most often in PTPN11 (5 patients).

To conclude, NGS is a powerful tool for the detection of acquired somatic mutations in patients with MDS and for early recognition of abnormal clones. In addition, incorporation of such tests can elucidate novel transformation processes, especially in the pediatric and young adult population for which such data is scarce.