Methylation analysis of DNA mismatch repair genes using DNA derived from the peripheral blood of patients with endometrial cancer: Epimutation in endometrial carcinogenesis

Takashi Takeda, Kouji Banno, Megumi Yanokura, Masataka Adachi, Moito Iijima, Haruko Kunitomi, Kanako Nakamura, Miho Iida, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

研究成果: Article

5 引用 (Scopus)

抄録

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 of MLH1, MSH2, and MSH6 promoter 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. MLH1 epimutation 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 with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation 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.

元の言語English
記事番号86
ジャーナルGenes
7
発行部数10
DOI
出版物ステータスPublished - 2016 10 14

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DNA Mismatch Repair
Endometrial Neoplasms
Methylation
Carcinogenesis
Microsatellite Instability
Germ-Line Mutation
DNA
Genes
Colorectal Neoplasms
Blood Cells
Hereditary Nonpolyposis Colorectal Neoplasms
Age of Onset
Genetic Promoter Regions
MutL Protein Homolog 1
Immunohistochemistry
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

これを引用

Methylation analysis of DNA mismatch repair genes using DNA derived from the peripheral blood of patients with endometrial cancer : Epimutation in endometrial carcinogenesis. / Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke.

:: Genes, 巻 7, 番号 10, 86, 14.10.2016.

研究成果: Article

Takeda, Takashi ; Banno, Kouji ; Yanokura, Megumi ; Adachi, Masataka ; Iijima, Moito ; Kunitomi, Haruko ; Nakamura, Kanako ; Iida, Miho ; Nogami, Yuya ; Umene, Kiyoko ; Masuda, Kenta ; Kobayashi, Yusuke ; Yamagami, Wataru ; Hirasawa, Akira ; Tominaga, Eiichiro ; Susumu, Nobuyuki ; Aoki, Daisuke. / Methylation analysis of DNA mismatch repair genes using DNA derived from the peripheral blood of patients with endometrial cancer : Epimutation in endometrial carcinogenesis. :: Genes. 2016 ; 巻 7, 番号 10.
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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 of MLH1, MSH2, and MSH6 promoter 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. MLH1 epimutation 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 with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation 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.",
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T1 - Methylation analysis of DNA mismatch repair genes using DNA derived from the peripheral blood of patients with endometrial cancer

T2 - Epimutation in endometrial carcinogenesis

AU - Takeda, Takashi

AU - Banno, Kouji

AU - Yanokura, Megumi

AU - Adachi, Masataka

AU - Iijima, Moito

AU - Kunitomi, Haruko

AU - Nakamura, Kanako

AU - Iida, Miho

AU - Nogami, Yuya

AU - Umene, Kiyoko

AU - Masuda, Kenta

AU - Kobayashi, Yusuke

AU - Yamagami, Wataru

AU - Hirasawa, Akira

AU - Tominaga, Eiichiro

AU - Susumu, Nobuyuki

AU - Aoki, Daisuke

PY - 2016/10/14

Y1 - 2016/10/14

N2 - 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 of MLH1, MSH2, and MSH6 promoter 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. MLH1 epimutation 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 with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation 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.

AB - 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 of MLH1, MSH2, and MSH6 promoter 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. MLH1 epimutation 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 with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation 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.

KW - Endometrial cancer

KW - Epimutation

KW - Lynch syndrome

KW - Methylation

KW - Mismatch repair genes

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