Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/137764
Title: GENOMIC INVESTIGATIONS OF CELLUAR AND MOLECULAR HETEROGENEITY IN GASTROINTESTINAL CANCERS
Authors: XING MANJIE
Keywords: Gastric cancer; genome; epigenome; TERT; EBF1
Issue Date: 8-Aug-2017
Citation: XING MANJIE (2017-08-08). GENOMIC INVESTIGATIONS OF CELLUAR AND MOLECULAR HETEROGENEITY IN GASTROINTESTINAL CANCERS. ScholarBank@NUS Repository.
Abstract: Expression of the catalytic subunit of telomerase reverse transcriptase (TERT) is low in human normal somatic cells. However, cells from more than 85% of human cancers transcriptionally reactivate TERT and this is necessary for cancer progression, including gastric cancer. The recent discovery of TERT promoter hotspot mutations in various cancers has provided insight into a plausible mechanism of telomerase reactivation. Copy number variants (CNV), structural variants (SV) were also reported to be associated with TERT overexpression in various types of cancer. However, the mechanism underlying TERT reactivation in gastric cancer has remained a mystery. Using whole genome sequencing (WGS), RNA-Seq, ChIP-Seq and methylation data for gastric cancer samples, transcription factor early B-cell factor (EBF1) was identified to function as a new tumor suppressor in gastric cancer and negatively regulating TERT. The results suggest there are multiple genomic and epigenomic mechanisms of disrupting EBF1 activity in gastric cancer, which in turn activates TERT.
URI: http://scholarbank.nus.edu.sg/handle/10635/137764
Appears in Collections:Ph.D Theses (Open)

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