アリタ　ミチツネ   Arita Michitsune   有田　通恒    所属   東邦大学  医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Genetic instability caused by loss of MutS homologue 3 in human colorectal cancer.
掲載誌名	正式名：Cancer research 略　 称：Cancer Res ISSNコード：00085472/15387445
掲載区分	国外
巻・号・頁	68(20),pp.8465-8472
著者・共著者	Haugen AC, Goel A, Yamada K†, Marra G, Nguyen TP, Nagasaka T, Kanazawa S†, Koike J†, Kikuchi Y, Zhong X, Arita M†, Shibuya K†, Oshimura M, Hemmi H†, Boland CR, Koi M
発行年月	2008/10
概要	Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency. High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however, its molecular basis is unclear. There is another type of MSI--elevated microsatellite alterations at selected tetranucleotide repeats (EMAST)--where loci containing [AAAG](n) or [ATAG](n) repeats are unstable. EMAST is frequent in non-CRCs; however, the incidence of EMAST and its cause in CRC is not known. Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non-MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non-MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average, 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of MSI at loci with dinucleotide repeats in CRC.
文献番号	PMID: 18922920
researchmap用URL	https://researchmap.jp/0713/