title: Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma.
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.
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Yann
authors.initials: Y
authors.lastname: Jamin
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Glass
authors.affiliation: Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Albert
authors.initials: A
authors.lastname: Hallsworth
authors.affiliation: Department of Pediatric Haematology and Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Rani
authors.initials: R
authors.lastname: George
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Dow-Mu
authors.initials: DM
authors.lastname: Koh
authors.affiliation: Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.affiliation: 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.
authors.forename: Louis
authors.initials: L
authors.lastname: Chesler
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D019943:Amino Acid Substitution; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D002648:Child; D002675:Child, Preschool; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D007223:Infant; D008297:Male; D008822:Mice, Transgenic; D020125:Mutation, Missense; D000071447:N-Myc Proto-Oncogene Protein; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C571825:MYCN protein, mouse; D000071447:N-Myc Proto-Oncogene Protein; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases