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International Journal of Clinical Oncology

Erschienen in:

11.06.2021 | Original Article

Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger

verfasst von: Takeshi Makabe, Wataru Yamagami, Akira Hirasawa, Izumi Miyabe, Tomokazu Wakatsuki, Mari Kikuchi, Akemi Takahashi, Junko Noda, Go Yamamoto, Daisuke Aoki, Kiwamu Akagi

Erschienen in: International Journal of Clinical Oncology | Ausgabe 9/2021

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Abstract

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.

[Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.

[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3’ untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.

[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

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Titel: Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger
verfasst von: Takeshi Makabe
Wataru Yamagami
Akira Hirasawa
Izumi Miyabe
Tomokazu Wakatsuki
Mari Kikuchi
Akemi Takahashi
Junko Noda
Go Yamamoto
Daisuke Aoki
Kiwamu Akagi
Publikationsdatum: 11.06.2021
Verlag: Springer Singapore
Erschienen in: International Journal of Clinical Oncology / Ausgabe 9/2021
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-021-01953-5

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Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger

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