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The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.
Parsa, Sara; Ortega-Molina, Ana; Ying, Hsia-Yuan; Jiang, Man; Teater, Matt; Wang, Jiahui; Zhao, Chunying; Reznik, Ed; Pasion, Joyce P; Kuo, David; Mohan, Prathibha; Wang, Shenqiu; Camarillo, Jeannie M; Thomas, Paul M; Jain, Neeraj; Garcia-Bermudez, Javier; Cho, Byoung-Kyu; Tam, Wayne; Kelleher, Neil L; Socci, Nicholas; Dogan, Ahmet; De Stanchina, Elisa; Ciriello, Giovanni; Green, Michael R; Li, Sheng; Birsoy, Kivanc; Melnick, Ari M; Wendel, Hans-Guido.
Afiliación
  • Parsa S; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Ortega-Molina A; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Ying HY; Department of Medicine and Weill Cornell Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Jiang M; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Teater M; Department of Medicine and Weill Cornell Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Wang J; The Jackson Laboratory Cancer Center, Farmington, CT, USA.
  • Zhao C; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Reznik E; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Pasion JP; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Kuo D; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
  • Mohan P; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Wang S; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Camarillo JM; Department of Chemistry, Molecular Biosciences and the National Resource for Translational and Developmental Proteomics, Northwestern University, Evanston, IL, USA.
  • Thomas PM; Department of Chemistry, Molecular Biosciences and the National Resource for Translational and Developmental Proteomics, Northwestern University, Evanston, IL, USA.
  • Jain N; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Garcia-Bermudez J; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Cho BK; Laboratory of Metabolic Regulation and Genetics, Rockefeller University, New York, NY, USA.
  • Tam W; Department of Chemistry, Molecular Biosciences and the National Resource for Translational and Developmental Proteomics, Northwestern University, Evanston, IL, USA.
  • Kelleher NL; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Socci N; Department of Chemistry, Molecular Biosciences and the National Resource for Translational and Developmental Proteomics, Northwestern University, Evanston, IL, USA.
  • Dogan A; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • De Stanchina E; Hematopathology Service, Departments of Pathology and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Ciriello G; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Green MR; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Li S; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Birsoy K; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Melnick AM; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wendel HG; The Jackson Laboratory Cancer Center, Farmington, CT, USA.
Nat Cancer ; 1: 653-664, 2020.
Article en En | MEDLINE | ID: mdl-33569544
ABSTRACT
Cancer cells adapt their metabolic activities to support growth and proliferation. However, increased activity of metabolic enzymes is not usually considered an initiating event in the malignant process. Here, we investigate the possible role of the enzyme serine hydroxymethyltransferase-2 (SHMT2) in lymphoma initiation. SHMT2 localizes to the most frequent region of copy number gains at chromosome 12q14.1 in lymphoma. Elevated expression of SHMT2 cooperates with BCL2 in lymphoma development; loss or inhibition of SHMT2 impairs lymphoma cell survival. SHMT2 catalyzes the conversion of serine to glycine and produces an activated one-carbon unit that can be used to support S-adenosyl methionine synthesis. SHMT2 induces changes in DNA and histone methylation patterns leading to promoter silencing of previously uncharacterized mutational genes, such as SASH1 and PTPRM. Together, our findings reveal that amplification of SHMT2 in cooperation with BCL2 is sufficient in the initiation of lymphomagenesis through epigenetic tumor suppressor silencing.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicina Hidroximetiltransferasa / Linfoma Límite: Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicina Hidroximetiltransferasa / Linfoma Límite: Humans Idioma: En Revista: Nat Cancer Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos