IMR Press / FBL / Volume 25 / Issue 4 / DOI: 10.2741/4834

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

SETD2, an epigenetic tumor suppressor: a focused review on GI tumor
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1 Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA
2 Department of Orthopaedics, Ruijin Hospital North, School of Medicine, Shanghai Jiaotong University, Shanghai, China
3 Department of Pathology, Third Central Hospital of Nankai University, Tianjin, China
4 Department of Pathology and Laboratory Medicine, Kaiser Permanente Sacramento Medical Center, Sacramento, CA, USA
Send correspondence to: Xiuli Liu, Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA, Tel: 352-265-7977, Fax: 352-627-9242, E-mail:
Front. Biosci. (Landmark Ed) 2020, 25(4), 781–797;
Published: 1 January 2020
(This article belongs to the Special Issue Epigenetics in development and cancer)

Significant progress has been made in our understanding of the role of epigenetic modifiers in many types of human cancer. Here, we review currently available studies on the unique histone methyltransferase, SETD2, which is responsible for H3 lysine 36 tri-methylation (H3K36me3). SETD2 plays pivotal roles in RNA alternative splicing regulation, DNA damage repair, and cytoskeleton protein methylation; inactivation of SETD2 and resultant dysregulation of these functions may lead to tumorigenesis. Despite being a newly discovered tumor suppressor, SETD2 has been found to be mutated in multiple types of cancer, including gastrointestinal tumor. Some tumors can acquire a selective growth advantage after SETD2 inactivation, which could happen in different stages in tumor progression. Decreased level of H3K36me3 caused by SETD2 inactivation has been shown to associate with higher tumor grade, tumor stage, metastasis risk, and shorter survival. Some studies also suggest that SETD2 mutation is associated with therapy resistance, therefore these SETD2-deficient tumors may need different therapeutic strategies.

RNA Alternative Splicing
Tubulin Methylation
DNA Damage Repair
Progression and Prognostic biomarker
Figure 1
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