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Title: Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer
Authors: Huang K.K.
Ramnarayanan K.
Zhu F.
Srivastava S.
Xu C.
Tan A.L.K.
Lee M.
Tay S.
Das K.
Xing M.
Fatehullah A.
Alkaff S.M.F.
Lim T.K.H.
Lee J.
Ho K.Y.
Rozen S.G.
Teh B.T.
Barker N.
Chia C.K.
Khor C.
Ooi C.J.
Fock K.M.
So J. 
Lim W.C.
Ling K.L.
Ang T.L.
Wong A.
Rao J.
Rajnakova A.
Lim L.G.
Yap W.M.
Teh M.
Yeoh K.G.
Tan P.
Keywords: cancer genomics
gastric cancer
Helicobacter pylori
intestinal metaplasia
risk stratification
Issue Date: 8-Jan-2018
Publisher: Cell Press
Citation: Huang K.K., Ramnarayanan K., Zhu F., Srivastava S., Xu C., Tan A.L.K., Lee M., Tay S., Das K., Xing M., Fatehullah A., Alkaff S.M.F., Lim T.K.H., Lee J., Ho K.Y., Rozen S.G., Teh B.T., Barker N., Chia C.K., Khor C., Ooi C.J., Fock K.M., So J., Lim W.C., Ling K.L., Ang T.L., Wong A., Rao J., Rajnakova A., Lim L.G., Yap W.M., Teh M., Yeoh K.G., Tan P. (2018-01-08). Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer. Cancer Cell 33 (1) : 137-150 e5. ScholarBank@NUS Repository.
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. Huang et al. perform molecular profiling of 138 intestinal metaplasias (IMs) from 148 gastric cancer (GC)-free patients and show that IMs with shortened telomeres and chromosomal alterations are associated with subsequent dysplasia or GC, whereas IMs with normal-like epigenomic patterns are associated with regression. � 2017 Elsevier Inc.
Source Title: Cancer Cell
ISSN: 15356108
DOI: 10.1016/j.ccell.2017.11.018
Appears in Collections:Staff Publications

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