Genomic information in cytology archives; Toward precision medicine for the most refractory cancers

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15963
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba University
• Principal Investigator: Ohyama Hiroshi 千葉大学, 医学部附属病院, 講師 (10814600)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん遺伝子 / 悪性新生物 / 遺伝子変異 / ゲノミクス / 膵癌 / 胆道癌

Outline of Final Research Achievements

There are limitations in obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling. We investigated whether archived cytological specimens (ACS) suit those tests. FFPE tissues and ACS from 44 patients with pancreaticobiliary disease were analyzed. We compared genomic profiles of FFPE and ACS from 19 patients with malignancies. We tested ACS from 25 patients for the ability to discriminate between malignant and benign disorders. We explored whether actionable and drug-matched mutations could be identified from ACS. Oncogenic mutations observed in ACS were 73% consistent with those identified in FFPE specimens. Genomic profiling using ACS discriminated malignant from benign disease with 93% accuracy, 91% sensitivity, and 100% specificity. Drug-matched mutations were identified in 32% of ACS and 21% of FFPE samples. In conclusion, ACS can discriminate malignancy and detect drug-matched mutations in patients with advanced pancreaticobiliary cancer.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、ACSは腫瘍組織と同様のゲノムプロファイルを有すること、ACSのゲノムプロファイリングにより高精度に良悪性を鑑別しうること、治療標的遺伝子変異の探索が可能であることが示された。ACSを用いてがんゲノムプロファイリングを実施することにより、最難治癌である胆膵癌の予後改善が期待される。胆膵癌で最も高頻度に検出されるKRAS変異については現在のところ有効な治療薬に乏しいが、薬剤開発の進展により恩恵を享受する対象が拡大することが期待される。