Intrinsic Susceptibility MRI Identifies Tumors with ALKF1174L Mutation in Genetically-Engineered Murine Models of High-Risk Neuroblastoma
Pearson, Andrew D. J.
Robinson, Simon P.
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CitationJamin, Yann, Laura Glass, Albert Hallsworth, Rani George, Dow-Mu Koh, Andrew D. J. Pearson, Louis Chesler, and Simon P. Robinson. 2014. “Intrinsic Susceptibility MRI Identifies Tumors with ALKF1174L Mutation in Genetically-Engineered Murine Models of High-Risk Neuroblastoma.” PLoS ONE 9 (3): e92886. doi:10.1371/journal.pone.0092886. http://dx.doi.org/10.1371/journal.pone.0092886.
AbstractThe early identification of children presenting ALKF1174L-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-ALKF1174L/Th-MYCN and the well-established Th-MYCN genetically-engineered murine models of neuroblastoma using MRI, we have identified a marked ALKF1174L-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 ALKF1174L 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 ALKF1174L mutation at the time of diagnosis.
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