Epigenetic inactivation of FAT4 contributes to gastric field cancerization

Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
Satoshi YoshidaToshikazu Ushijima

Abstract

Gastric cancer (GC) is highly influenced by aberrant methylation, and accumulation of aberrant methylation in gastric mucosae produces an epigenetic field for cancerization. Nevertheless, the individual driver genes involved in such field cancerization are still unclear. Here, we aimed to demonstrate that FAT4, a novel tumor suppressor identified by exome sequencing of GC, is methylation-silenced and that such methylation is involved in epigenetic field cancerization for GC. A transcription start site was determined by the 5' rapid amplification of complementary DNA ends method. DNA methylation was analyzed by bisulfite sequencing with use of a next-generation sequencer or quantitative methylation-specific PCR. Gene expression was analyzed by quantitative reverse transcription PCR. A single transcription start site was identified for FAT4 in gastric epithelial cells, and a CpG island was located in the FAT4 promoter region. FAT4 was highly methylated in two of 13 GC cell lines and was not expressed in them. Removal of FAT4 methylation by a DNA demethylating agent (5-aza-2'-deoxycytidine) restored its expression in the two cell lines. In primary GC samples, FAT4 was methylated in 12 of 82 GCs (14.6 %). FAT4 methylation was assoc...Continue Reading

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Citations

Mar 15, 2016·Cancer Letters·Yoshifumi BabaHideo Baba
Oct 4, 2016·Journal of Cell Communication and Signaling·Maryam Pilehchian LangroudiHaleh Akhavan-Niaki
Jan 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Satoshi YamashitaToshikazu Ushijima
Jul 6, 2019·Frontiers in Genetics·Adenilson PereiraÂndrea Ribeiro-Dos-Santos
Mar 17, 2017·British Journal of Cancer·Yanjing SongLin Chen
Jul 19, 2018·World Journal of Gastroenterology : WJG·Tasuku Matsuoka, Masakazu Yashiro
May 13, 2021·Best Practice & Research. Clinical Gastroenterology·Gianluca BusinelloMatteo Fassan

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