Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis
by
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 and Daisuke Aoki
, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu and Daisuke Aoki
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Nora Nock
Genes 2016, 7(10), 86; https://doi.org/10.3390/genes7100086
Received: 7 July 2016 / Revised: 28 August 2016 / Accepted: 6 October 2016 / Published: 14 October 2016
(This article belongs to the Special Issue Cancer Genetics)
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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MDPI and ACS Style
Takeda, T.; Banno, K.; Yanokura, M.; Adachi, M.; Iijima, M.; Kunitomi, H.; Nakamura, K.; Iida, M.; Nogami, Y.; Umene, K.; Masuda, K.; Kobayashi, Y.; Yamagami, W.; Hirasawa, A.; Tominaga, E.; Susumu, N.; Aoki, D. 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, 7, 86.
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