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基于C-CAT数据库的胰腺癌中与可操作基因畸变相关的因素。

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

作者信息

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

机构信息

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.

Department of Clinical Oncology, The University of Tokyo Hospital, Tokyo, Japan.

出版信息

J Gastroenterol. 2025 May 2. doi: 10.1007/s00535-025-02253-9.

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) (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, 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.

摘要

背景

综合基因组分析(CGP)检测越来越多地用于探索实体瘤的基因组匹配疗法。本研究的目的是利用来自高级癌症基因组治疗中心(C-CAT)数据库的真实世界数据,调查与胰腺癌(PC)中可操作基因畸变相关的因素。

方法

在2019年6月至2023年7月期间登记在C-CAT数据库中的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)进行基于组织的CGP检测的患者。我们调查了可操作基因畸变的发生率及其检测相关因素。

结果

该队列包括3554例接受F1CDx检测的患者和1128例接受NOP检测的患者,50%的病例采用手术标本。腺癌是主要亚型(95%),90%的病例发现KRAS突变。可操作基因畸变的总体发生率为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)(比值比[OR]1.87,95%置信区间[CI]1.00-2.67)、KRAS野生型(KRAS)(OR 3.09,95%CI 2.49-3.85)和使用F1CDx(OR 2.38,95%CI 1.98-2.85)与可操作基因畸变显著相关。

结论

在ACC、KRAS和使用F1CDx的病例中,可操作基因畸变的可能性更大。CGP检测的选择应根据具体情况进行,因为除了可操作基因畸变之外,还需要考虑其他因素。

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