Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer.

IF 3.8 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Report Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.1093/gastro/goae092

Fu-Rong Kou, Jian Li, Zheng-Hang Wang, Ting Xu, Juan-Juan Qian, En-Li Zhang, Li-Jun Zhang, Lin Shen, Xi-Cheng Wang

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Abstract

Background: The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer (CRC). Published data on gene fusions are limited by relatively small sample sizes, with a primary focus on Western populations. This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.

Methods: This study included 5,534 consecutive CRC patients from the Genecast database. Genomic profiling was performed using a panel of 769 cancer-related genes. Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.

Results: Among 5,534 CRC patients, 54 (0.98%) had actionable gene fusions, with NTRK1/2/3 being the most common fusion (0.38%), accounting for 38.9% (21/54) of those with fusions. Actionable gene fusion enrichment was higher in patients with microsatellite instability-high (MSI-H) (6.7% vs. 0.5%, P < 0.001), RAS/BRAF wildtype (2.0% vs. 0.2%, P < 0.001) and RNF43 mutation (7.7% vs. 0.4%, P < 0.001) than in patients with microsatellite stability/MSI-low, RAS/BRAF mutation and RNF43 wildtype, respectively. When these markers were combined, the fusion detection rate increased. Among patients with RAS/BRAF wildtype and MSI-H, fusions were detected in 20.3% of patients. The fusion detection rate further increased to 37.5% when RNF43 mutation was added. The fusion detection rate was also higher in colon cancer than in rectal cancer. No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast, cBioPortal, and ChimerSeq databases.

Conclusions: Approximately 1% of the unselected Chinese CRC population carries actionable gene fusions, mostly involving NTRK. Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.

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大样本中国结直肠癌患者可操作基因融合分析。

背景：在未经筛选的结直肠癌（CRC）患者中，基因融合的发生率极低。已发表的基因融合数据受限于相对较小的样本量，且主要集中于西方人群。本研究旨在分析大量中国连续CRC人群中的可操作基因融合：本研究纳入了 Genecast 数据库中的 5,534 例连续的 CRC 患者。方法：该研究纳入了 Genecast 数据库中的 5,534 名连续的 CRC 患者，使用 769 个癌症相关基因组成的基因组图谱进行分析。同时还从 cBioPortal 和 ChimerSeq 中收集了 34 例有可操作基因融合的 CRC 患者的数据：结果：在 5,534 例 CRC 患者中，有 54 例（0.98%）存在可操作基因融合，其中 NTRK1/2/3 是最常见的融合基因（0.38%），占融合患者的 38.9%（21/54）。微卫星不稳定性高（MSI-H）（6.7% vs. 0.5%，P 0.001）、RAS/BRAF 野生型（2.0% vs. 0.2%，P 0.001）和 RNF43 突变（7.7% vs. 0.4%，P 0.001）患者的可检测基因融合富集率分别高于微卫星稳定性/MSI-低、RAS/BRAF 突变和 RNF43 野生型患者。当这些标记物合并使用时，融合检出率增加。在RAS/BRAF野生型和MSI-H患者中，20.3%的患者检测到融合。加入 RNF43 突变后，融合检出率进一步上升至 37.5%。结肠癌的融合检出率也高于直肠癌。在Genecast、cBioPortal和ChimerSeq数据库中，可检测基因融合患者的临床或分子特征没有发现明显差异：结论：在未入选的中国 CRC 患者中，约有 1%携带可操作基因融合，其中大部分涉及 NTRK。可操作基因融合在 MSI-H、RAS/BRAF 野生型或 RNF43 突变的 CRC 以及结肠癌中更为普遍。绘制这些分子标记可显著提高融合检测率，从而帮助临床医生选择融合检测和靶向治疗的候选者。

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

Gastroenterology Report Medicine-Gastroenterology

CiteScore

4.60

自引率

2.80%

发文量

审稿时长

8 weeks

期刊介绍： Gastroenterology Report is an international fully open access (OA) online only journal, covering all areas related to gastrointestinal sciences, including studies of the alimentary tract, liver, biliary, pancreas, enteral nutrition and related fields. The journal aims to publish high quality research articles on both basic and clinical gastroenterology, authoritative reviews that bring together new advances in the field, as well as commentaries and highlight pieces that provide expert analysis of topical issues.