| Literature DB >> 29290541 |
Kie Kyon Huang1, Kalpana Ramnarayanan1, Feng Zhu2, Supriya Srivastava3, Chang Xu4, Angie Lay Keng Tan1, Minghui Lee1, Suting Tay1, Kakoli Das1, Manjie Xing5, Aliya Fatehullah6, Syed Muhammad Fahmy Alkaff7, Tony Kiat Hon Lim7, Jonathan Lee8, Khek Yu Ho9, Steven George Rozen1, Bin Tean Teh1, Nick Barker10, Chung King Chia11, Christopher Khor12, Choon Jin Ooi12, Kwong Ming Fock13, Jimmy So14, Wee Chian Lim11, Khoon Lin Ling12, Tiing Leong Ang13, Andrew Wong15, Jaideepraj Rao16, Andrea Rajnakova17, Lee Guan Lim18, Wai Ming Yap19, Ming Teh20, Khay Guan Yeoh21, Patrick Tan22.
Abstract
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%). Several IMs exhibited hypermethylation at DNA methylation valleys; however, IMs generally lack intragenic hypomethylation signatures of advanced malignancy. IM patients with shortened telomeres and chromosomal alterations were associated with subsequent dysplasia or GC; conversely patients exhibiting normal-like epigenomic patterns were associated with regression.Entities:
Keywords: Helicobacter pylori; cancer genomics; gastric cancer; intestinal metaplasia; risk stratification
Mesh：
Year: 2017 PMID： 29290541 DOI： 10.1016/j.ccell.2017.11.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743