title: Mir-449a, a potential diagnostic biomarker for WNT group of medulloblastoma.
abstract: Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The 5 year disease-free survival rate is rather low. There is a consensus that MB can be divided into at least four clinically, transcriptionally, and genetically distinct molecular variants, being designated as wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4. It poses a great challenge to the design of therapeutic strategy for MB patients. Intensive clinical intervention, including high dose radiotherapy, is commonly used in treatment of high risk MB, most of which are considered to be Group 3 patients. But such intensive therapy should be avoided to protect neurologic function of patients in the lower risk WNT group. In present study, MB subgroup assignment in formalin-fixed paraffin embedded (FFPE) specimens from 45 Chinese patients were performed by Nanostring platform using 22 well-known signature genes. Based on comparative expression profiles of miRNA real-time PCR microarray in MB cells with and without treatment of demethylation reagent, as well as MSP assay, miR-449a was demonstrated to be significantly silenced by aberrant DNA methylation in tumor cells. Real-time PCR showed that expression level of miR-449a in WNT group was significantly different from other subgroups, although it was down-regulated in most of the MB samples. In conclusion, current study demonstrates for the first time the feasibility of using the Nanostring assay for subgrouping of MBs in Chinese patients. In addition, MiR-449a, a candidate tumor suppressor regulated by hypermethylation, is a novel potential diagnostic marker for WNT group of MBs.
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China.
authors.forename: Yongxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China.|Department of Neuropathology, University of Washington, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Xue Yuan Road 38#, Beijing, 100191, China. qingchang@bjmu.edu.cn.
authors.forename: Qing
authors.identifier: 0000-0001-5138-8760
authors.initials: Q
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D015415:Biomarkers; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis* / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D051153:Wnt Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins
keywords: Hypermethylation; Medulloblastoma; Molecular subtype; Nanostring assay