CLINICAL IMPLICATIONS OF COPY NUMBER ALTERATION DETECTION USING PANEL-BASED NEXT-GENERATION SEQUENCING DATA IN MYELODYSPLASTIC SYNDROME

Abstract

Introduction: Recurrent somatic mutations are found in about 90 % of the MDS patients, and some of the mutations are known to have a prognostic value at various clinical stages of myelodysplastic syndrome (MDS). However, there are no specific guidelines for the assessment of CNAs, and the CNA test is not included in standard practice in the diagnosis and prognostication of MDS. Thus, there is a need to evaluate whether the detection of CNAs, in addition to genetic mutations, has clinical significance. In this study. Methods: Targeted deep sequencing of 28 well-known MDS-related genes was performed for 266 patients with MDS. DNA copy number was estimated using the targeted deep sequencing data. Results: Overall, 215 (80.8 %) patients were found to have at least one somatic mutation; 67 (25.2 %) had at least one CNA; 227 (85.3 %) had either a somatic mutation or CNA; and 12 had CNA without somatic mutations. Considering the clinical variables and somatic mutations alone, multivariate analysis demonstrated that sex, revised International Prognostic Scoring System (IPSS-R), and NRAS and TP53 mutations were independent prognostic factors for overall survival. For AML-free survival, these factors were sex, IPSS-R, and mutations in NRAS, DNMT3A, and complex karyotype/TP53 mutations. When we consider clinical variables along with somatic mutations and CNAs, genetic alterations in TET2, LAMB4, U2AF1, and CBL showed additional significant impact on the survivals. Conclusions: In conclusion, our study suggests that the concurrent detection of somatic mutations and targeted CNAs may provide clinically useful information for the prognosis of MDS patients.