Factors associated with actionable gene aberrations in pancreatic cancer based on the C-CAT database.

IF 6.9 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Journal of Gastroenterology Pub Date : 2025-08-01 Epub Date: 2025-05-02 DOI:10.1007/s00535-025-02253-9

Go Endo, Kazunaga Ishigaki, Yousuke Nakai, Hiroto Nishio, Koshiro Fukuda, Kota Ishida, Shinya Takaoka, Yurie Tokito, Rintaro Fukuda, Kensaku Noguchi, Hiroki Oyama, Tatsunori Suzuki, Tatsuya Sato, Tomotaka Saito, Tsuyoshi Hamada, Koji Miyabayashi, Naminatsu Takahara, Yasuyoshi Sato, Hidenori Kage, Katsutoshi Oda, Mitsuhiro Fujishiro

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引用次数: 0

Abstract

Background: Comprehensive genomic profiling (CGP) tests are increasingly used to explore the genomically matched therapies for solid tumors. The aim of this study is to investigate factors associated with actionable gene aberrations in pancreatic cancer (PC) using real-world data from the Center for Advanced Cancer Genome Therapy (C-CAT) database.

Methods: Among 6768 patients with unresectable and recurrent PC registered in the C-CAT database between June 2019 and July 2023, we identified 4628 patients who underwent tissue-based CGP tests using either FoundationOne^® CDx (F1CDx) or OncoGuide^™ NCC Oncopanel (NOP). We investigated the incidence of actionable gene aberrations and the factors associated with their detection.

Results: The cohort included 3,554 patients who underwent F1CDx and 1128 NOP, with surgical specimens in 50% of the cases. Adenocarcinoma was the predominant subtype (95%), and KRAS mutations were found in 90%. The overall incidence of actionable gene aberrations was 27%. The most common gene abnormalities were BRCA2 (3.4%), followed by ATM (2.9%), ERBB2 (2.8%), PIK3 CA (2.5%), and BRAF (1.9%). Multivariable analysis revealed that acinar cell carcinoma (ACC) (Odds ratio [OR] 1.87, 95% confidence interval [CI] 1.00-2.67), KRAS wild type (KRAS_WT) (OR 3.09, 95% CI 2.49-3.85), and use of F1CDx (OR 2.38, 95% CI 1.98-2.85) were significantly associated with actionable gene aberrations.

Conclusions: Actionable gene aberrations were more likely in cases of ACC, KRAS_WT, and F1CDx usage. The choice of CGP test should be made on a case-by-case basis, as other factors beyond actionable gene aberrations also need to be considered.

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基于C-CAT数据库的胰腺癌可操作基因畸变相关因素。

背景：综合基因组分析（CGP）测试越来越多地用于探索实体肿瘤的基因组匹配疗法。本研究的目的是利用来自晚期癌症基因组治疗中心（C-CAT）数据库的真实世界数据，研究胰腺癌（PC）中与可操作基因畸变相关的因素。方法：在2019年6月至2023年7月期间在C-CAT数据库中登记的6768例不可切除和复发性PC患者中，我们确定了4628例使用FoundationOne®CDx （F1CDx）或OncoGuide™NCC Oncopanel （NOP）进行组织基CGP检查的患者。我们调查了可操作基因畸变的发生率及其检测相关的因素。结果：该队列包括3554例接受F1CDx和1128例NOP的患者，其中50%的病例有手术标本。腺癌为主要亚型（95%），KRAS突变占90%。可操作基因畸变的总发生率为27%。最常见的基因异常是BRCA2(3.4%)，其次是ATM（2.9%）、ERBB2（2.8%）、PIK3 CA（2.5%）和BRAF（1.9%）。多变量分析显示，腺泡细胞癌（ACC）（优势比[OR] 1.87, 95%可信区间[CI] 1.00-2.67）、KRAS野生型（KRASWT）（优势比[OR] 3.09, 95% CI 2.49-3.85）和F1CDx的使用（优势比[OR] 2.38, 95% CI 1.98-2.85）与可操作基因畸变显著相关。结论：ACC、KRASWT和F1CDx患者更可能出现可操作的基因畸变。CGP检测的选择应根据具体情况进行，因为除可操作的基因畸变外的其他因素也需要考虑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

12.20

自引率

1.60%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.