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PLoS ONE | Vol.9, Issue.3 | 2017-05-29 | Pages

PLoS ONE

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

Dow-Mu Koh,Simon P Robinson,Andrew D J Pearson,Yann Jamin,Laura Glass,Albert Hallsworth,Rani George,Louis Chesler  
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.

Original Text (This is the original text for your reference.)

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

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.

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Dow-Mu Koh,Simon P Robinson,Andrew D J Pearson,Yann Jamin,Laura Glass,Albert Hallsworth,Rani George,Louis Chesler,.Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.. 9 (3),.

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