Genetic alterations in early-onset pancreatic cancer
Project/Area Number |
17K09451
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Asahikawa Medical College |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
水上 裕輔 医療法人徳洲会札幌東徳洲会病院医学研究所, がん研究部, 部門長 (30400089)
小野 裕介 医療法人徳洲会札幌東徳洲会病院医学研究所, 臨床生体情報解析部, 部門長 (40742648)
田中 宏樹 旭川医科大学, 医学部, 助教 (70596155)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 膵癌 / 感受性遺伝子 / 若年発症 / コピー数変異 / 体細胞変異解析 / 次世代シーケンサー / コピー数多型 / メチル化解析 / 癌 / 遺伝子 / 細胞・組織 / 臨床 |
Outline of Final Research Achievements |
This study aimed to examine novel genetic alterations that are useful for predicting the onset of pancreatic cancer. Fifty-two early-onset Japanese pancreatic cancer patients who developed the disease under the age of 50 were enrolled, and exome sequencing was performed to identify pathogenic germline variants. Three potential susceptibility genes were found. A reanalysis of publicly available somatic mutation data, including 109 cases from UT Southwestern Medical Center, identified a significant number of copy number mutations in young-onset cases. Using tumor-normal tissue pair from our Japanese cohort, we validated the abnormality was more frequently observed in the early onset cases relative to average aged patients. Our findings will support the algorithm's basis to predict subjects who are at high risk of developing pancreatic cancer.
|
Academic Significance and Societal Importance of the Research Achievements |
膵癌の発症年齢中央値は70歳台前半であるが、30-40歳台の若年発症を稀に見る。これまでに、BRCA1/2, CDKN2A, STK11など、複数の膵癌感受性遺伝子が一部同定されており、ゲノム異常の全貌を明らかにすることは、膵発癌の高危険群を特定する重要な情報と考えられる。自験例から得た新規の膵癌感受性遺伝子に関わる情報、及び既存データベースの再解析結果を基に、膵癌発症の高危険群を絞り込むためのアルゴリズムを構築し、その臨床的な意義を今後検証する。
|
Report
(4 results)
Research Products
(17 results)
-
-
-
-
-
[Journal Article] Genetic analysis of postoperative recurrence of pancreatic cancer potentially owing to needle tract seeding during EUS-FNB.2019
Author(s)
Kawabata H, Miyazawa Y, Sato H, Okada T, Hayashi A, Iwama T, Fujibayashi S, Goto T, Sasajima J, Takauji S, Fujiya M, Torimoto Y, Tanino M, Omori Y, Ono Y, Karasaki H, Mizukami Y, Okumura T.
-
Journal Title
Endosc Int Open.
Volume: 7(12)
Issue: 12
Pages: E1768-E1772
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient.2019
Author(s)
Kashima S, Tanabe H, Tanino M, Kobayashi Y, Murakami Y, Iwama T, Sasaki T, Kunogi T, Takahashi K, Ando K, Ueno N, Moriichi K, Fukudo M, Tasaki Y, Hosokawa M, Mizukami Y, Fujiya M, Okumura T.
-
Journal Title
Front Oncol.
Volume: 9
Pages: 1375-1375
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] ARF6 and AMAP1 are major targets of KRAS and TP53 mutations to promote invasion, PD-L1 dynamics and immune evasion of pancreatic cancer2019
Author(s)
Hashimoto, S*., Furukawa, S*., Hashimoto, A*., Tsutaho, A., Fukao, A., Sakamura, Y., Parajuli, G., Onodera, Y., Otsuka, Y., Handa, H., Oikawa, T., Hata, S., Nishikawa Y., Mizukami, Y., Kodama, Y., Murakami M., Fujiwara, T., Hirano, S., and Sabe, H. (*Equally contributed)
-
Journal Title
Proceedings of the National Academy of the Sciences of the United States of America
Volume: 116
Issue: 35
Pages: 17450-17459
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
[Presentation] Capturing Pancreatic Tumor-derived Mutations from Fine Needle Aspiration Using Digital PCR.2019
Author(s)
Ono Y, Hayashi A, Wada R, Suzuki M, Maeda C, Okada T, Sato H, Kawabata H, Goto T, Karasaki H, Mizukami Y, Okumura T.
Organizer
The 50th Anniversary Joint Meeting of APA & JPS
Related Report
Int'l Joint Research
-
[Presentation] The Temporal Order of KRAS and GNAS Mutations in Intraductal Papillary Mucinous Neoplasms of the Pancreas and Evolution to Invasive Carcinoma.2019
Author(s)
Mizukami Y, Karasaki H, Ono Y, Omori Y, Hayashi A, Tachibana S, Sugiyama Y, Sato H, Kawabata H, Goto T, Fujiya M, Takahashi K, Katanuma A, Maguchi H, Furukawa T, Okumura T.
Organizer
The 50th Anniversary Joint Meeting of APA & JPS
Related Report
Int'l Joint Research
-
-
[Presentation] ABNORMAL ACTIVATION OF HNRNPA0 INHIBITS CANCER CELL APOPTOSIS AND PROMOTES EXCESSIVE MITOSIS IN CANCER CELLS.2019
Author(s)
Konishi H, Fujiya M, Kita A, Tanaka H, Kashima S, Sakatani A, Dokoshi T, Ando K, Ueno N, Moriichi K, Iwama T, Takahashi K, Murakami Y, Ikuta K, Mizukami Y, Goto T, Okumura T.
Organizer
DDW2019米国消化器病週間
Related Report
Int'l Joint Research