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A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2

Journal of Human Genetics volume 68, pages 783–787 (2023)Cite this article

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Abstract

Germline double heterozygosity (GDH) is rarely reported in cases of inherited cancer syndromes, and GDH of a mismatch repair gene and BRCA has never been reported in Japan. Nonetheless, the current report demonstrates a case of ovarian mucinous adenocarcinoma with initiated Lynch syndrome (LS)-related surveillance because of a known germline MSH2 variant. Six and a half years after oophorectomy, multiple tumors developed in the patient’s lungs, bones, and lymph nodes, and histology results confirmed mucinous adenocarcinoma. Systemic chemotherapy including an anti-PD-L1 antibody was effective for >1 year, but brain metastases developed. Pathology of the brain tumors showed mucinous adenocarcinoma without expression of MSH2 and MSH6, while multi-gene panel testing demonstrated not only high microsatellite instability and a high tumor mutation burden, but also germline BRCA2 variants. Further, germline testing in relatives confirmed both variants were from the paternal line, from which many LS-related cancers develop, but not BRCA-related cancer.

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Acknowledgements

The authors thank the all staffs of the expert panel in the Shizuoka Cancer Center Hospital. This study was supported by JSPS KAKENHI (grant number 19K19372 to YK).

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Authors and Affiliations

  1. Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan

    Rina Harada, Hiroyuki Matsubayashi, Yoshimi Kiyozumi, Nobuhiro Kado, Seiichiro Nishimura & Satomi Higashigawa

  2. Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan

    Hiroyuki Matsubayashi, Kenichiro Imai & Yoichi Yamamoto

  3. Division of Respiratory Medicine, Shizuoka Cancer Center, Shizuoka, Japan

    Haruki Kobayashi

  4. Division of Brain Surgery, Shizuoka Cancer Center, Shizuoka, Japan

    Koichi Mitsuya

  5. Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan

    Takuma Oishi

  6. Clinical Research Center of Shizuoka Cancer Center, Shizuoka, Japan

    Masakuni Serizawa

Authors
  1. Rina Harada
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  2. Hiroyuki Matsubayashi
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  3. Yoshimi Kiyozumi
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  4. Haruki Kobayashi
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  5. Koichi Mitsuya
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  7. Yoichi Yamamoto
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  8. Takuma Oishi
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  9. Nobuhiro Kado
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  10. Seiichiro Nishimura
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  11. Satomi Higashigawa
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  12. Masakuni Serizawa
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Contributions

RH and HM wrote manuscript. HK, KM, and HM clinically managed the patients. YK, RH, SH, and HM performed genetic counselling. KI, YY, and HM performed endoscopic procedures. TO made pathological diagnosis. NK, SN, and MS provided suggestive advises in writing the manuscript.

Corresponding author

Correspondence to Hiroyuki Matsubayashi.

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The authors declare no competing interests.

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A written informed consent for the publication was obtained from the patient.

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Harada, R., Matsubayashi, H., Kiyozumi, Y. et al. A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2. J Hum Genet 68, 783–787 (2023). https://doi.org/10.1038/s10038-023-01178-6

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  • DOI: https://doi.org/10.1038/s10038-023-01178-6

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