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Licensed Unlicensed Requires Authentication Published by De Gruyter March 1, 2013

Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in human healthy and tumoral liver

  • Hélène Pellanda EMAIL logo


Carcinogenesis is a multi-step and multifactorial process. It includes genetic, epigenetic, nutritional and environmental factors, which are closely interconnected. Human hepatocellular carcinoma (HCC) is among the most frequent and lethal cancers. Imbalance in the S-adenosylmethionine (SAM) concentration, the main methyl group donor, strongly influences the development of HCC. Key enzymes of carbon metabolism are greatly reduced in patients with cirrhosis and HCC. These alterations play a role in genetic instability and epigenetic modifications (DNA methylation, and histone modifications), however, the molecular underlying mechanisms are still poorly understood. We aimed to investigate betaine homocysteine methyltransferase (BHMT) expression in HepG2 cells and human hepatocarcinoma tissues. Tumor and surrounding healthy tissue were compared. HepG2 cells and tumor samples showed a strong decrease in BHMT transcripts resulting from the transcription of a splicing variant that contained a frameshift mutation generating a premature termination codon and gene loss of function. This splicing variant, not detected in normal adult and fetal liver, cannot be explained by any mechanism involving the known splicing consensus sequences. BHMT activity was abolished in HepG2 cells and protein expression was detected neither in HepG2 cells nor in five of the six tumor samples investigated. Further investigation is needed to elucidate whether this abnormal BHMT transcription is part of cause or consequence of liver carcinogenesis.

Corresponding author: Hélène Pellanda, INSERM U 954, Faculté de Médecine – BP 184, 54511 Vandoeuvre les Nancy, France, Phone: +333 83 683292, Fax: +333 83 683279

Acknowledgments: Financial support to complete this work was provided by the Ligue Contre le Cancer (Grant project CIRCE), France.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.


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Received: 2012-10-11
Accepted: 2012-11-30
Published Online: 2013-03-01
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

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