title: Incidence and prognostic impact of DNMT3A mutations in Korean normal karyotype acute myeloid leukemia patients.
abstract: BACKGROUND
  DNA methyltransferase 3A (DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact of DNMT3A mutations in Korean NK AML patients.
  
  
  METHODS
  Total 67 NK AML patients diagnosed during the recent 10 years were enrolled. DNMT3A mutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based on in silico analysis results. Clinical features and prognosis were compared with respect to DNMT3A mutation status.
  
  
  RESULTS
  Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs. DNMT3A NSVs, DMs, and R882 mutation were identified in 14.9%-17.9%, 10.3%-10.4%, and 7.5% of patients, respectively. DNMT3A mutations were frequently detected in FLT3 ITD mutated patients (P=0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly.
  
  
  CONCLUSIONS
  Incidences of DNMT3A NSVs, DMs, and R882 mutation are 14.9%-17.9%, 10.3%-10.4%, and 7.5%, respectively, in Korean NK AML patients. DNMT3A mutations are associated with FLT3 ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients.
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea ; Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Sang Hyuk
authors: SH
authors: Park
authors: Department of Laboratory Medicine, Hanmaeum Hospital, 21 Woni-daero, 682 Beon-gil, Seongsan-gu, Changwon-si, Gyeongsangnam-do 642-832, Republic of Korea.
authors: Jae-Cheol
authors: JC
authors: Choi
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea ; Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Shine Young
authors: SY
authors: Kim
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea ; Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Jongyoun
authors: J
authors: Yi
authors: Department of Laboratory Medicine, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan 614-735, Republic of Korea.
authors: Seung Hwan
authors: SH
authors: Oh
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 626-770, Republic of Korea.
authors: In-Suk
authors: IS
authors: Kim
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea ; Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Hyung-Hoi
authors: HH
authors: Kim
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 626-770, Republic of Korea.
authors: Chulhun Ludgerus
authors: CL
authors: Chang
authors: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea ; Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Eun Yup
authors: EY
authors: Lee
authors: Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Moo-Kon
authors: MK
authors: Song
authors: Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Ho-Jin
authors: HJ
authors: Shin
authors: Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.
authors: Joo Seop
authors: JS
authors: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C000717967:DNMT3A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
references: Trends Biochem Sci. 2000 Jun;25(6):300-2
references: 10838572
references: Leuk Res. 2013 Nov;37(11):1488-94
references: 24054719
references: Cancer Res. 2001 Oct 1;61(19):7233-9
references: 11585760
references: Blood. 2002 Oct 15;100(8):2717-23
references: 12351377
references: Blood. 2002 Dec 15;100(13):4325-36
references: 12393746
references: Hematol J. 2002;3(6):283-9
references: 12522450
references: J Clin Oncol. 2004 Feb 15;22(4):624-33
references: 14726504
references: Blood. 1998 Oct 1;92(7):2322-33
references: 9746770
references: Blood. 2005 Dec 1;106(12):3740-6
references: 16051734
references: Blood. 2005 Dec 1;106(12):3733-9
references: 16076867
references: Blood. 2005 Dec 1;106(12):3747-54
references: 16109776
references: Blood. 2008 Feb 1;111(3):1552-9
references: 17940205
references: Cell Stem Cell. 2009 Oct 2;5(4):442-9
references: 19796624
references: J Clin Oncol. 2010 Jun 1;28(16):2739-47
references: 20439648
references: J Clin Oncol. 2010 Aug 1;28(22):3636-43
references: 20567020
references: Blood. 2010 Sep 23;116(12):2122-6
references: 20538800
references: Blood. 2010 Nov 4;116(18):3622-6
references: 20656931
references: N Engl J Med. 2010 Dec 16;363(25):2424-33
references: 21067377
references: Nat Genet. 2011 Apr;43(4):309-15
references: 21399634
references: J Clin Oncol. 2011 Jul 20;29(21):2889-96
references: 21670448
references: Blood. 2011 Nov 17;118(20):5593-603
references: 21881046
references: Eur J Haematol. 2012 Feb;88(2):128-35
references: 21967546
references: Blood. 2012 Jan 12;119(2):559-68
references: 22077061
references: Semin Oncol. 2012 Feb;39(1):109-22
references: 22289497
references: J Clin Oncol. 2012 Mar 1;30(7):742-50
references: 22291079
references: Cancer. 2012 May 15;118(10):2665-73
references: 22020636
references: Leukemia. 2012 Jun;26(6):1247-54
references: 22289988
references: J Natl Compr Canc Netw. 2012 Aug;10(8):984-1021
references: 22878824
references: Int J Lab Hematol. 2012 Oct;34(5):502-9
references: 22494415
references: APMIS. 2013 Feb;121(2):85-94
references: 23031157
references: Blood. 2001 Apr 15;97(8):2434-9
references: 11290608