Risk-Reducing Genetic Variant of Wilms Tumor 1 Gene rs16754 in Korean Patients With BCR-ABL1-Negative Myeloproliferative Neoplasm

Ann Lab Med. 2015 May;35(3):348-51. doi: 10.3343/alm.2015.35.3.348. Epub 2015 Apr 1.

Abstract

The genetic variant rs16754 of Wilms tumor gene 1 (WT1) has recently been described as an independent prognostic factor in AML patients. It is of great interest to test whether WT1 single nucleotide polymorphism can be used as a molecular marker in other types of cancer, to improve risk and treatment stratification. We performed sequencing analysis of exons 7 and 9 of WT1, which are known mutational hotspots, in a total of 73 patients with BCR-ABL1-negative myeloproliferative neoplasm (MPN) and 93 healthy controls. No previously reported WT1 mutations were identified in the present study. In Korean patients with BCR-ABL1-negative MPN, WT1 genetic variant rs16754 had no significant impact on clinical outcomes. We observed a significant difference in the allelic frequencies of WT1 rs16754 in Koreans between BCR-ABL1-negative MPN cases and healthy controls. Individuals carrying variant G alleles of WT1 rs16754 showed a relatively low prevalence of BCR-ABL1-negative MPN, compared with those carrying wild A alleles of WT1 rs16754 (Hazard ratio 0.10-0.65, P<0.05). Therefore, possession of the variant G allele of WT1 rs16754 may reduce the risk of developing BCR-ABL1-negative MPN.

Keywords: Myeloproliferative neoplasm; WT1; rs16754.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People / genetics*
  • Case-Control Studies
  • Exons
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Gene Frequency
  • Genotype
  • Humans
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Proportional Hazards Models
  • Republic of Korea
  • Risk
  • Sequence Analysis, DNA
  • WT1 Proteins / genetics*
  • Young Adult

Substances

  • BCR-ABL1 fusion protein, human
  • WT1 Proteins
  • WT1 protein, human
  • Fusion Proteins, bcr-abl