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

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

Author information

1
Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
2
Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom; Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.
3
Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
4
Department of Pediatric Haematology and Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America.
5
Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.

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.

PMID:
24667968
PMCID:
PMC3965493
DOI:
10.1371/journal.pone.0092886
[Indexed for MEDLINE]
Free PMC Article

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