Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma

PLoS One. 2014 Mar 25;9(3):e92886. doi: 10.1371/journal.pone.0092886. eCollection 2014.

Abstract

The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. In comparing the radiology of the novel Th-ALK(F1174L)/Th-MYCN and the well-established Th-MYCN genetically-engineered murine models of neuroblastoma using MRI, we have identified a marked ALK(F1174L)-driven vascular phenotype. We demonstrate that quantitation of the transverse relaxation rate R2* (s(-1)) using intrinsic susceptibility-MRI under baseline conditions and during hyperoxia, can robustly discriminate this differential vascular phenotype, and identify MYCN-driven tumors harboring the ALK(F1174L) mutation with high specificity and selectivity. Intrinsic susceptibility-MRI could thus potentially provide a non-invasive and clinically-exploitable method to help identifying children with MYCN-driven neuroblastoma harboring the ALK(F1174L) mutation at the time of diagnosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Anaplastic Lymphoma Kinase
  • Animals
  • Child
  • Child, Preschool
  • Female
  • Genetic Engineering*
  • Humans
  • Infant
  • Male
  • Mice, Transgenic
  • Mutation, Missense*
  • N-Myc Proto-Oncogene Protein
  • Neoplasms, Experimental* / genetics
  • Neoplasms, Experimental* / metabolism
  • Neoplasms, Experimental* / pathology
  • Neuroblastoma* / genetics
  • Neuroblastoma* / metabolism
  • Neuroblastoma* / pathology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases* / genetics
  • Receptor Protein-Tyrosine Kinases* / metabolism

Substances

  • MYCN protein, mouse
  • N-Myc Proto-Oncogene Protein
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases