Genetic alterations in early-onset pancreatic cancer

2019 Fiscal Year Final Research Report

• 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: Sasajima Junpei 旭川医科大学, 医学部, 客員講師 (80451467)
• 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
• Keywords: 膵癌 / 感受性遺伝子 / 若年発症

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.

Free Research Field

消化器内科、がんゲノム、遺伝学

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。