Format

Send to

Choose Destination
Front Biosci (Landmark Ed). 2020 Jan 1;25:781-797.

SETD2, an epigenetic tumor suppressor: a focused review on GI tumor.

Author information

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.
5
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA, xiuliliu@ufl.edu.

Abstract

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.

PMID:
31585917

Supplemental Content

Loading ...
Support Center