| Project/Area Number |
18K08557
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
|
|---|
| Research Institution | Chiba Cancer Center (Research Institute) |
|---|
Principal Investigator |
NAKAMURA RIKIYA 千葉県がんセンター(研究所), その他部局等, その他 (50456026)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
横井 左奈 千葉県がんセンター(研究所), 遺伝子診断部, 部長 (30372452)
山本 尚人 千葉県がんセンター(研究所), 乳腺外科, 部長 (40506169)
末永 雄介 千葉県がんセンター(研究所), 発がん研究グループ 発がん制御研究部, 研究員 (80581793)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 遺伝性乳癌 / 乳癌 / 遺伝性腫瘍 / BRCA2 / 卵巣癌 |
|---|
| Outline of Final Research Achievements |
Pathogenic variants in the tumor suppressor gene BRCA2 increase the incidence of breast and ovarian cancer and cause hereditary breast and ovarian cancer syndrome (HBOC). Recently, we discovered a novel BRCA2 missense variant of uncertain significance in a patient with a family history of breast cancer. The variant was inherited within the family, and the sister and father carrying the variant developed breast and pancreatic cancer, respectively. The location of the variant is on a oligonucleotide binding domain of BRCA2 that is essential for DNA binding. In this study, we biochemically verified the reduction of the homologous recombination activity for DNA double strand break. We also used genome editing to generate knock-in mice with the novel variant. As a result, reproductive organ abnormalities and ovarian tumor were observed in one strain.
|
| Academic Significance and Societal Importance of the Research Achievements |
生まれながらにBRCA2の病的変異を有することは遺伝性乳癌卵巣癌症候群の確定診断となり、体質に合った抗がん剤の選択や、将来の癌リスクに対して早期からの精密検診、高リスク臓器の予防的切除といった対処法を選択できる。本研究により、これまで病的意義が不明であったBRCA2ミスセンス変異が病的であるとわかると、本人のみならず、きょうだいやこどもが同じ体質を共有するか診断でき、癌治療の選択肢を増やしたり、将来の癌リスクに対する予防が可能になるため、癌の生存率の改善に寄与し、医療経済にも貢献すると期待される。
|
