title: Characterization of anaplastic lymphoma kinase-positive medulloblastomas.
abstract: Medulloblastomas are the most common pediatric malignant primary brain tumor. To our knowledge, there are no known critical and druggable tyrosine kinases in medulloblastomas, precluding the use of established tyrosine kinase inhibitors that have shown efficacy in other tumor types. We studied the expression of anaplastic lymphoma kinase (ALK), a well-characterized tyrosine kinase and drug target, in a cohort of medulloblastomas by immunohistochemistry, and identified three ALK-positive cases. Mutational analyses did not reveal a definite underlying genetic mechanism for the ALK expression, although one of the cases showed increased ALK copy number. Our findings have clinical implications and warrant further pharmacological and functional studies, as well as evaluation in larger patient cohorts, to fully characterize the value of ALK as a prognostic and predictive therapeutic marker in medulloblastomas.
authors.affiliation: Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Hospital, National University Health System, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. Electronic address: tranceblues@gmail.com.
authors.forename: Benedict
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
authors.forename: Chik Hong
authors.initials: CH
authors.lastname: Kuick
authors.affiliation: Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Lim
authors.affiliation: Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
authors.forename: Min Hwee
authors.initials: MH
authors.lastname: Yong
authors.affiliation: Department of Pathology, National University Hospital, National University Health System, Singapore.
authors.forename: Chi Kuen
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, National Neuroscience Institute, Singapore.
authors.forename: Sharon Y Y
authors.initials: SYY
authors.lastname: Low
authors.affiliation: Neurosurgical Services, KK Women's and Children's Hospital, Singapore.
authors.forename: David C Y
authors.initials: DCY
authors.lastname: Low
authors.affiliation: Department of Pathology, National University Hospital, National University Health System, Singapore.
authors.forename: Diana
authors.initials: D
authors.lastname: Lim
authors.affiliation: Haematology/Oncology Service, Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore.
authors.forename: Shui Yen
authors.initials: SY
authors.lastname: Soh
authors.affiliation: Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
authors.forename: Kenneth T E
authors.initials: KTE
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Immunohistochemistry; Medulloblastoma; Tyrosine kinase