title: Clinicopathological characteristics, molecular subgrouping, and expression of miR-379/miR-656 cluster (C14MC) in adult medulloblastomas.
abstract: Medulloblastoma (MB) is a childhood tumor comprising four molecular subgroups: WNT, SHH, group 3 and group 4, with diagnostic and prognostic connotations. Very few studies are available on molecular subgrouping of adult MBs due to their rarity. Recently, loss of chromosome14q has been reported in SHH MBs, with downregulation of miR-379/miR-656 cluster (C14MC) in pediatric SHH MBs. Hence, the present study on adult MBs was undertaken to enumerate clinicopathological characteristics and molecular subgroups, and to analyze expression of C14MC and its transcriptional regulators, MEF2, JUN and ESRRG. Immunohistochemistry for β-catenin, GAB1 and YAP1 was performed to identify molecular subgroups. MYC amplification was evaluated by FISH. Expression profiling of 47 miRNAs from C14MC was performed using customized Taqman low-density array. Expression of transcriptional regulators was examined using RT-PCR. Seventy-one adult MBs were analyzed. They had male predominance and majority were located laterally (52 %). A significant proportion of cases were of Desmoplastic/nodular histology (32 %); MBEN was not seen. WNT tumors constituted 4.2 %, SHH 62 %, and non-WNT/non-SHH 33.8 %. MYC amplification was identified in 11.1 % cases. Patient outcome was worse in adults. Significant downregulation of C14MC was observed in all MB subgroups, and MEF-2 expression was downregulated. Adult MBs are distinct from childhood MBs in terms of location, histopathological subtypes, molecular subgroups, as well as prognosis. Silencing of C14MC in all MB subgroups suggests its role as a tumor suppressor locus in tumorigenesis. Deregulation of C14MC can possibly be attributed to repression of MEF2.
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Kavneet
authors: K
authors: Kaur
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Aanchal
authors: A
authors: Kakkar
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Anupam
authors: A
authors: Kumar
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Suvendu
authors: S
authors: Purkait
authors: Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.
authors: Supriya
authors: S
authors: Mallick
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Vaishali
authors: V
authors: Suri
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors: Mehar C
authors: MC
authors: Sharma
authors: Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.
authors: Pramod K
authors: PK
authors: Julka
authors: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors: Deepak
authors: D
authors: Gupta
authors: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors: Ashish
authors: A
authors: Suri
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India. sarkar.chitra@gmail.com.
authors: Chitra
authors: C
authors: Sarkar
mesh_terms: D000328:Adult; D000368:Aged; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D064326:MEF2 Transcription Factors / Q000378:metabolism; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051153:Wnt Proteins / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D053823:Hedgehog Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Adult; C14MC; Medulloblastoma; Molecular subgroups; miRNA