title: RAS mutation analysis in a large cohort of Chinese patients with acute myeloid leukemia.
abstract: OBJECTIVE
  We examined RAS mutational status and correlated this with presenting morphology, cytogenetics, clinical outcome and other gene aberrations in a large cohort of Chinese acute myeloid leukemia (AML) patients.
  
  
  METHODS
  N-RAS and K-RAS were screened for mutations at hot-spot codons 12, 13 and 61 using high resolution melting analysis (HRMA) and direct DNA sequencing in 504 Chinese AML patients and their clinical relevance was analyzed.
  
  
  RESULTS
  The frequencies of mutations of N-RAS and K-RAS were 9.7% (49/504) and 2.9% (15/504), respectively. c.35G>A (rs121913237: G>A; p.Gly12Asp and rs121913529: G>A; p.Gly12Asp) and c.38G>A (rs121434596: G>A; p.Gly13Asp and rs112445441: G>A; p.Gly13Asp) were the most common base substitutions (46% in N-RAS and 60% in K-RAS, respectively). AML patients with RAS mutations presented significantly higher white blood cell count (WBC) at diagnosis than those without mutations (p<0.001). RAS mutations were underrepresented in patients with t(15;17) (2.9%, p=0.01), while overrepresented in cases with abn11q23 (50%, p=0.002) and inv(16) (66.6%, p=0.04). In the FAB subtypes M4 and M5, RAS mutations were more frequent (21.6% and 20.6%, respectively) than they were in other subtypes (7.5%, p=0.006 and 0.005, respectively). FLT3-ITD and RAS mutation were rarely coexistent (p=0.03). RAS mutation didn't influence overall survival (OS) either in the entire cohort or within some defined subgroups.
  
  
  CONCLUSIONS
  RAS mutations are associated with some biologically specific subtypes of AML but don't impact clinical outcome in Chinese patients.
authors: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu Province, 215006, PR China.
authors: Xiaofei
authors: X
authors: Yang
authors: Jun
authors: J
authors: Qian
authors: Aining
authors: A
authors: Sun
authors: Jiang
authors: J
authors: Lin
authors: Gaofei
authors: G
authors: Xiao
authors: Jia
authors: J
authors: Yin
authors: Suning
authors: S
authors: Chen
authors: Depei
authors: D
authors: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D003062:Codon; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis
chemical_list: D003062:Codon