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...

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Main Authors: Yann Jamin, Laura Glass, Albert Hallsworth, Rani George, Dow-Mu Koh, Andrew D J Pearson, Louis Chesler, Simon P Robinson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092886&type=printable
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author Yann Jamin
Laura Glass
Albert Hallsworth
Rani George
Dow-Mu Koh
Andrew D J Pearson
Louis Chesler
Simon P Robinson
author_facet Yann Jamin
Laura Glass
Albert Hallsworth
Rani George
Dow-Mu Koh
Andrew D J Pearson
Louis Chesler
Simon P Robinson
author_sort Yann Jamin
collection DOAJ
description 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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spelling doaj-art-3608f06eb2fe4373837a3d9879ed56802025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9288610.1371/journal.pone.0092886Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.Yann JaminLaura GlassAlbert HallsworthRani GeorgeDow-Mu KohAndrew D J PearsonLouis CheslerSimon P RobinsonThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092886&type=printable
spellingShingle Yann Jamin
Laura Glass
Albert Hallsworth
Rani George
Dow-Mu Koh
Andrew D J Pearson
Louis Chesler
Simon P Robinson
Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
PLoS ONE
title Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
title_full Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
title_fullStr Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
title_full_unstemmed Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
title_short Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
title_sort intrinsic susceptibility mri identifies tumors with alkf1174l mutation in genetically engineered murine models of high risk neuroblastoma
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092886&type=printable
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