The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.
Document Type
Article
Publication Date
6-2020
Keywords
JGM
JAX Source
Nat Cancer 2020 Jun; 1:653-664
Volume
1
First Page
653
Last Page
664
ISSN
2662-1347
PMID
33569544
DOI
https://doi.org/10.1038/s43018-020-0080-0
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 SHMT2cooperates 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.
Recommended Citation
Parsa S,
Ortega-Molina A,
Ying H,
Jiang M,
Teater M,
Wang J,
Zhao C,
Reznik E,
Pasion J,
Kuo D,
Mohan P,
Wang S,
Camarillo J,
Thomas P,
Jain N,
Garcia-Bermudez J,
Cho B,
Tam W,
Kelleher N,
Socci N,
Dogan A,
De Stanchina E,
Ciriello G,
Green M,
Li S,
Birsoy K,
Melnick A,
Wendel H.
The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing. Nat Cancer 2020 Jun; 1:653-664