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CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.

ABSTRACT: Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity.

SUBMITTER: Spence T

PROVIDER: S-EPMC4159569 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.

Spence Tara T Sin-Chan Patrick P Picard Daniel D Barszczyk Mark M Hoss Katharina K Lu Mei M Kim Seung-Ki SK Ra Young-Shin YS Nakamura Hideo H Fangusaro Jason J Hwang Eugene E Kiehna Erin E Toledano Helen H Wang Yin Y Shi Qing Q Johnston Donna D Michaud Jean J La Spina Milena M Buccoliero Anna Maria AM Adamek Dariusz D Camelo-Piragua Sandra S Peter Collins V V Jones Chris C Kabbara Nabil N Jurdi Nawaf N Varlet Pascale P Perry Arie A Scharnhorst David D Fan Xing X Muraszko Karin M KM Eberhart Charles G CG Ng Ho-Keung HK Gururangan Sridharan S Van Meter Timothy T Remke Marc M Lafay-Cousin Lucie L Chan Jennifer A JA Sirachainan Nongnuch N Pomeroy Scott L SL Clifford Steven C SC Gajjar Amar A Shago Mary M Halliday William W Taylor Michael D MD Grundy Richard R Lau Ching C CC Phillips Joanna J Bouffet Eric E Dirks Peter B PB Hawkins Cynthia E CE Huang Annie A

Acta neuropathologica 20140520 2

Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group ...[more]

PMID: 24839957

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Dataset Information

CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.

Publications

CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.

Similar Datasets

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