title: Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia.
abstract: Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells.
  
  
  
  We performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sample pairs from Korean patients with de novo AML. We explored the functional impact of the genes identified in the mutational analyses through an integrated Gene Ontology (GO) and pathway analysis.
  
  
  
  A total of 11 genes, including NEFH (p = 6.27 × 10-13and q = 1.18 × 10-8) and TMPRSS13 (p = 1.40 × 10-10and q = 1.32 × 10-6), also demonstrated q values less than 0.1 in 36 Korean AML patients. Five out of the 11 novel genes have previously been reported to be associated with other cancers. Two gene mutations, CEBPA (p = 5.22 × 10-5) and ATXN3 (p = 9.75 × 10-4), showed statistical significance exclusively in the M2 and M3 subtypes of the French-American-British classifications, respectively. A total of 501 genes harbored 478 missense, 22 nonsense, 93 frameshift indels, and/or three stop codon deletions and these gene mutations significantly enriched GO terms for signal transduction (GO:0007165, p = 1.77 × 10-3), plasma membrane (GO:0005886, p = 3.07 × 10-4), and scaffold protein binding (GO:0097110, p = 8.65 × 10-4). The mitogen-activated protein kinase (hsa04010, 7.67 × 10-4) was the most enriched Kyoto Encyclopedia of Genes and Genomes pathway.
  
  
  
  Morphological AML subtypes may in part reflect subtype specific patterns of genomic alterations. Following validation, future studies to evaluate the usefulness of these genes in genetic testing for the early diagnosis and prognostic prediction of AML patients would be worthwhile.
authors.affiliation: Department of Medical Genetics, College of Medicine, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do, 24252, Republic of Korea.|Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea.
authors.forename: Seong Gu
authors.initials: SG
authors.lastname: Heo
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Omics Core Lab., National Cancer Center, Goyang, Republic of Korea.|The Catholic University, Seoul, Republic of Korea.
authors.forename: Jong Kwang
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Syntekabio Inc., Seoul, Republic of Korea.
authors.forename: Jongsun
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Hyung-Lae
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Medical Genetics, College of Medicine, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do, 24252, Republic of Korea. jwpark@hallym.ac.kr.
authors.forename: Ji Wan
authors.identifier: 0000-0003-0840-1696
authors.initials: JW
authors.lastname: Park
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods*; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D056910:Republic of Korea; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D018389:Codon, Nonsense; D009363:Neoplasm Proteins
keywords: Acute myeloid leukemia; Gene ontology; Pathway analysis; Somatic mutation; Subtype-specific mutation; Whole-exome sequencing