The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing Journal Article


Authors: Parsa, S.; Ortega-Molina, A.; Ying, H. Y.; Jiang, M.; Teater, M.; Wang, J.; Zhao, C.; Reznik, E.; Pasion, J. P.; Kuo, D.; Mohan, P.; Wang, S.; Camarillo, J. M.; Thomas, P. M.; Jain, N.; Garcia-Bermudez, J.; Cho, B. K.; Tam, W.; Kelleher, N. L.; Socci, N.; Dogan, A.; De Stanchina, E.; Ciriello, G.; Green, M. R.; Li, S.; Birsoy, K.; Melnick, A. M.; Wendel, H. G.
Article Title: The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing
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. Parsa et al. report a mechanism of lymphoma initiation involving cooperation of BCL2 and increased activity of the metabolic enzyme SHMT2, which imparts changes in DNA and histone methylation.
Keywords: metabolism; cell survival; chromosome 9p; dna methylation; c-myc; deletions; mechanisms; catabolism; inactivation; synthesis pathway
Journal Title: Nature Cancer
Volume: 1
Issue: 6
ISSN: 2662-1347
Publisher: Nature Research  
Date Published: 2020-06-01
Start Page: 653
End Page: 664
Language: English
ACCESSION: WOS:000614874300012
DOI: 10.1038/s43018-020-0080-0
PROVIDER: wos
PMCID: PMC7872152
PUBMED: 33569544
Notes: Article -- Source: Wos
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MSK Authors
  1. Nicholas D Socci
    266 Socci
  2. Hans Guido Wendel
    102 Wendel
  3. Chunying Zhao
    7 Zhao
  4. Man Jiang
    20 Jiang
  5. Shenqiu Wang
    7 Wang
  6. Ahmet Dogan
    468 Dogan
  7. Eduard Reznik
    108 Reznik
  8. Prathibha Mohan
    13 Mohan
  9. Sara   Parsa
    4 Parsa
  10. Joyce Penelope Pasion
    5 Pasion