Abstract：
:A field for cancerization, or a field defect, is formed by the accumulation of genetic and epigenetic alterations in normal-appearing tissues, and is involved in various cancers, especially multiple cancers. Epigenetic alterations are frequently present in chronic inflammation-exposed tissues, but information on individual genes involved in the formation of a field defect is still fragmental. Here, using non-cancerous gastric tissues of cancer patients, we isolated 16 aberrantly methylated genes, and identified chromatin remodelers ACTL6B and SMARCA1 as novel genes frequently methylated in non-cancerous tissues. SMARCA1 was expressed at high levels in normal gastric tissues, but was frequently silenced by aberrant methylation in gastric cancer cells. Moreover, somatic mutations of additional chromatin remodelers, such as ARID1A, SMARCA2, and SMARCA4, were found in 30% of gastric cancers. Mutant allele frequency suggested that the majority of cancer cells harbored a mutation when present. Depletion of a chromatin remodeler, SMARCA1 or SMARCA2, in cancer cell lines promoted their growth. These results showed that epigenetic and genetic alterations of chromatin remodelers are induced at an early stage of carcinogenesis and are frequently involved in the formation of a field defect.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Takeshima H,Niwa T,Takahashi T,Wakabayashi M,Yamashita S,Ando T,Inagawa Y,Taniguchi H,Katai H,Sugiyama T,Kiyono T,Ushijima Tdoi
10.1016/j.canlet.2014.11.038subject
Has Abstractpub_date
2015-02-01 00:00:00pages
328-338issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(14)00709-5journal_volume
357pub_type
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