title: N-ras mutation detection by pyrosequencing in adult patients with acute myeloid leukemia at a single institution.
abstract: BACKGROUND
  N-ras mutations are one of the most commonly detected abnormalities of myeloid origin. N-ras mutations result in a constitutively active N-ras protein that induces uncontrolled cell proliferation and inhibits apoptosis. We analyzed N-ras mutations in adult patients with AML at a particular institution and compared pyrosequencing analysis with a direct sequencing method for the detection of N-ras mutations.
  
  
  METHODS
  We analyzed 90 bone marrow samples from 83 AML patients. We detected N-ras mutations in codons 12, 13, and 61 using the pyrosequencing method and subsequently confirmed all data by direct sequencing. Using these methods, we screened the N-ras mutation quantitatively and determined the incidence and characteristic of N-ras mutation.
  
  
  RESULTS
  The incidence of N-ras mutation was 7.2% in adult AML patients. The patients with N-ras mutations showed significant higher hemoglobin levels (P=0.022) and an increased incidence of FLT3 mutations (P=0.003). We observed 3 cases with N-ras mutations in codon 12 (3.6%), 2 cases in codon 13 (2.4%), and 1 case in codon 61 (1.2%). All the mutations disappeared during chemotherapy.
  
  
  CONCLUSIONS
  There is a low incidence (7.2%) of N-ras mutations in AML patients compared with other populations. Similar data is obtained by both pyrosequencing and direct sequencing. This study showed the correlation between the N-ras mutation and the therapeutic response. However, pyrosequencing provides quantitative data and is useful for monitoring therapeutic responses.
authors.affiliation: Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Ji Hun
authors.initials: JH
authors.lastname: Jeong
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Moon Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Pil Whan
authors.initials: PW
authors.lastname: Park
authors.forename: Yiel Hea
authors.initials: YH
authors.lastname: Seo
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.forename: Junshik
authors.initials: J
authors.lastname: Hong
authors.forename: Jeong Yeal
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism; D003062:Codon; D020732:Cytogenetic Analysis; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D003062:Codon; D006454:Hemoglobins; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D018631:ras Proteins
keywords: AML; Bone marrow; N-ras; Pyrosequencing