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Ten-eleven translocation protein 1 modulates medulloblastoma progression.
Kim, Hyerim; Kang, Yunhee; Li, Yujing; Chen, Li; Lin, Li; Johnson, Nicholas D; Zhu, Dan; Robinson, M Hope; McSwain, Leon; Barwick, Benjamin G; Yuan, Xianrui; Liao, Xinbin; Zhao, Jie; Zhang, Zhiping; Shu, Qiang; Chen, Jianjun; Allen, Emily G; Kenney, Anna M; Castellino, Robert C; Van Meir, Erwin G; Conneely, Karen N; Vertino, Paula M; Jin, Peng; Li, Jian.
Afiliación
  • Kim H; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Kang Y; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Li Y; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Chen L; Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Lin L; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Johnson ND; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Zhu D; Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Robinson MH; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • McSwain L; Department of Pediatric Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Barwick BG; Department of Pediatric Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Yuan X; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Liao X; Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
  • Zhao J; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Zhang Z; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Shu Q; Hydrocephalus Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Chen J; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Allen EG; Hydrocephalus Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Kenney AM; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Castellino RC; Hydrocephalus Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Van Meir EG; The Children's Hospital and Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
  • Conneely KN; Department of Systems Biology and Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA, 91010, USA.
  • Vertino PM; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Jin P; Department of Pediatric Oncology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Li J; Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Genome Biol ; 22(1): 125, 2021 04 29.
Article en En | MEDLINE | ID: mdl-33926529
BACKGROUND: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes. RESULTS: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes. CONCLUSIONS: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas / Susceptibilidad a Enfermedades / Oxigenasas de Función Mixta / Meduloblastoma Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas / Susceptibilidad a Enfermedades / Oxigenasas de Función Mixta / Meduloblastoma Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido