Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer
Takashi Mitamura,1 Tianyue Zhai,1 Kanako C Hatanaka,2 Yutaka Hatanaka,2,3 Toraji Amano,4 Lei Wang,5,6 Shinya Tanaka,5,6 Hidemichi Watari1 1Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 2Center for Development of Advan...
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Dove Medical Press
2022-11-01
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| Series: | Pharmacogenomics and Personalized Medicine |
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| Online Access: | https://www.dovepress.com/germline-prdm1-variant-rs2185379-in-long-term-recurrence-free-survivor-peer-reviewed-fulltext-article-PGPM |
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| author | Mitamura T Zhai T Hatanaka KC Hatanaka Y Amano T Wang L Tanaka S Watari H |
| author_facet | Mitamura T Zhai T Hatanaka KC Hatanaka Y Amano T Wang L Tanaka S Watari H |
| author_sort | Mitamura T |
| collection | DOAJ |
| description | Takashi Mitamura,1 Tianyue Zhai,1 Kanako C Hatanaka,2 Yutaka Hatanaka,2,3 Toraji Amano,4 Lei Wang,5,6 Shinya Tanaka,5,6 Hidemichi Watari1 1Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 2Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 3Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 4Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan; 5Institute for Chemical Reaction Design and Discovery, Hokkaido University, Sapporo, Hokkaido, Japan; 6Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, JapanCorrespondence: Takashi Mitamura, Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, North15, West 7, Kita-Ku, Sapporo, 0608638, Hokkaido, Japan, Tel +81 11 706 5941, Fax +81 11 706 7711, Email takami@huhp.hokudai.ac.jpPurpose: To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients.Patients and Methods: DNA specimens were obtained from rare long-term recurrence-free survivors with FIGO stage III–IV ovarian cancer with no recurrence for 8– 23 years after primary treatments for a whole-genome analysis of approximately 660,000 single nucleotide variants. We then established a mouse model with a notable gene alteration by CRISPR/Cas9 to confirm the biological role.Results: The long-term recurrence-free survivors more frequently had germline heterozygous variant rs2185379 of the PRDM1 gene exon than patients with early recurrence (6.8-fold, P=0.013) and the general population. In the mouse model, primary intraperitoneal disseminated tumors of allograft ID8 were significantly smaller in the germline heterozygous rs2185379 group than in the wild-type group (57.4% decrease, P=0.008). Immunohistochemistry showed that the area of distribution of infiltrating T lymphocytes with positive CD8 staining was significantly increased in the germline heterozygous rs2185379 group in comparison to the wild-type group.Conclusion: Germline heterozygous rs2185379 in PRDM1 is correlated with an excellent prognosis and can be used to establish a new strategy for treating advanced ovarian cancer.Keywords: ovarian cancer, long-term survivors, rs2185379, PRDM1 |
| first_indexed | 2024-04-11T07:58:29Z |
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| institution | Directory Open Access Journal |
| issn | 1178-7066 |
| language | English |
| last_indexed | 2024-04-11T07:58:29Z |
| publishDate | 2022-11-01 |
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| series | Pharmacogenomics and Personalized Medicine |
| spelling | doaj.art-9d0f2fbaf66d4dabb4c13b03819af0f02022-12-22T04:35:52ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662022-11-01Volume 1597798479960Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian CancerMitamura TZhai THatanaka KCHatanaka YAmano TWang LTanaka SWatari HTakashi Mitamura,1 Tianyue Zhai,1 Kanako C Hatanaka,2 Yutaka Hatanaka,2,3 Toraji Amano,4 Lei Wang,5,6 Shinya Tanaka,5,6 Hidemichi Watari1 1Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 2Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 3Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 4Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan; 5Institute for Chemical Reaction Design and Discovery, Hokkaido University, Sapporo, Hokkaido, Japan; 6Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, JapanCorrespondence: Takashi Mitamura, Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, North15, West 7, Kita-Ku, Sapporo, 0608638, Hokkaido, Japan, Tel +81 11 706 5941, Fax +81 11 706 7711, Email takami@huhp.hokudai.ac.jpPurpose: To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients.Patients and Methods: DNA specimens were obtained from rare long-term recurrence-free survivors with FIGO stage III–IV ovarian cancer with no recurrence for 8– 23 years after primary treatments for a whole-genome analysis of approximately 660,000 single nucleotide variants. We then established a mouse model with a notable gene alteration by CRISPR/Cas9 to confirm the biological role.Results: The long-term recurrence-free survivors more frequently had germline heterozygous variant rs2185379 of the PRDM1 gene exon than patients with early recurrence (6.8-fold, P=0.013) and the general population. In the mouse model, primary intraperitoneal disseminated tumors of allograft ID8 were significantly smaller in the germline heterozygous rs2185379 group than in the wild-type group (57.4% decrease, P=0.008). Immunohistochemistry showed that the area of distribution of infiltrating T lymphocytes with positive CD8 staining was significantly increased in the germline heterozygous rs2185379 group in comparison to the wild-type group.Conclusion: Germline heterozygous rs2185379 in PRDM1 is correlated with an excellent prognosis and can be used to establish a new strategy for treating advanced ovarian cancer.Keywords: ovarian cancer, long-term survivors, rs2185379, PRDM1https://www.dovepress.com/germline-prdm1-variant-rs2185379-in-long-term-recurrence-free-survivor-peer-reviewed-fulltext-article-PGPMovarian cancerlong-term survivorsrs2185379prdm1 |
| spellingShingle | Mitamura T Zhai T Hatanaka KC Hatanaka Y Amano T Wang L Tanaka S Watari H Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer Pharmacogenomics and Personalized Medicine ovarian cancer long-term survivors rs2185379 prdm1 |
| title | Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer |
| title_full | Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer |
| title_fullStr | Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer |
| title_full_unstemmed | Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer |
| title_short | Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer |
| title_sort | germline prdm1 variant rs2185379 in long term recurrence free survivors of advanced ovarian cancer |
| topic | ovarian cancer long-term survivors rs2185379 prdm1 |
| url | https://www.dovepress.com/germline-prdm1-variant-rs2185379-in-long-term-recurrence-free-survivor-peer-reviewed-fulltext-article-PGPM |
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