Mutation profiling of 19 candidate genes in acute myeloid leukemia suggests significance of<i>DNMT3A</i>mutations

Abstract

// Sang-Yong Shin 1 , Seung-Tae Lee 2 , Hee-Jin Kim 3 , Eun Hae Cho 5 , Jong-Won Kim 3 , Silvia Park 4 , Chul Won Jung 4 , Sun-Hee Kim 3 1 Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea 2 Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea 3 Department of Laboratory Medicine &amp; Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Green Cross Genome, Yongin, Korea Correspondence to: Seung-Tae Lee, email: lee.st@yuhs.ac Sun-Hee Kim, email: sunnyhk@skku.edu Keywords: acute myeloid leukemia, mutation, next generation sequencing, DNMT3A Received: October 19, 2015&emsp;&emsp;&emsp;&emsp; Accepted: May 13, 2016&emsp;&emsp;&emsp;&emsp; Published: June 23, 2016 ABSTRACT We selected 19 significantly-mutated genes in AMLs, including FLT3 , DNMT3A, NPM1, TET2, RUNX1, CEBPA, WT1, IDH1, IDH2, NRAS, ASXL1, SETD2, PTPN11, TP53, KIT, JAK2, KRAS, BRAF and CBL , and performed massively parallel sequencing for 114 patients with acute myeloid leukemias, mainly including those with normal karyotypes (CN-AML). More than 80% of patients had at least one mutation in the genes tested. DNMT3A mutation was significantly associated with adverse outcome in addition to conventional risk stratification such as the European LeukemiaNet (ELN) classification. We observed clinical usefulness of mutation testing on multiple target genes and the association with disease subgroups, clinical features and prognosis in AMLs.