title: Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.
abstract: Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation ofMLH1,MSH2, andMSH6promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation.MLH1epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient withMLH1epimutation showed high level MSI (MSI-H), loss ofMLH1expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation ofMSH2orMSH6. TheMLH1epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. double.tak@keio.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. kbanno@z7.keio.jp.
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. meguyano@keio.jp.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yanokura
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. madachi1014@keio.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. moito.not.for.sale@gmail.com.
authors.forename: Moito
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. harukoirie1225@gmail.com.
authors.forename: Haruko
authors.initials: H
authors.lastname: Kunitomi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. konakaramukana0101@hotmail.co.jp.
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. mihoiida1029@gmail.com.
authors.forename: Miho
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. yuya22wing@hotmail.com.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nogami
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. umekiyo@hotmail.co.jp.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Umene
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. masuken1106@gmail.com.
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. kobax@a2.keio.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. gami@z8.keio.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamagami
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. hir-aki@z8.keio.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. tominaga@a3.keio.jp.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tominaga
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. susumu35@a6.keio.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Susumu
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan. aoki@z7.keio.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
keywords: Lynch syndrome; endometrial cancer; epimutation; methylation; mismatch repair genes