Yamamoto Hiroyuki, Arai Hiroyuki, Oikawa Ritsuko, Umemoto Kumiko, Takeda Hiroyuki, Mizukami Takuro, Kubota Yohei, Doi Ayako, Horie Yoshiki, Ogura Takashi, Izawa Naoki, Moore Jay A, Sokol Ethan S, Sunakawa Yu
Department of Bioinformatics, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Department of Gastroenterology, St. Marianna University School of Medicine, Kawasaki, Japan.
Target Oncol. 2024 May;19(3):459-471. doi: 10.1007/s11523-024-01052-1. Epub 2024 Apr 13.
Panel-based comprehensive genomic profiling is used in clinical practice worldwide; however, large real-world datasets of patients with advanced gastric cancer are not well known.
We investigated what differences exist in clinically relevant alterations for molecularly defined or age-stratified subgroups.
This was a collaborative biomarker study of a real-world dataset from comprehensive genomic profiling testing (Foundation Medicine, Inc.). Hybrid capture was carried out on at least 324 cancer-related genes and select introns from 31 genes frequently rearranged in cancer. Overall, 4634 patients were available for analyses and were stratified by age (≥ 40/< 40 years), microsatellite instability status, tumor mutational burden status (high 10 ≥ /low < 10 Muts/Mb), Epstein-Barr virus status, and select gene alterations. We analyzed the frequency of alterations with a chi-square test with Yate's correction.
Genes with frequent alterations included TP53 (60.1%), ARID1A (19.6%), CDKN2A (18.2%), KRAS (16.6%), and CDH1 (15.8%). Differences in comprehensive genomic profiling were observed according to molecularly defined or age-stratified subgroups. Druggable genomic alterations were detected in 31.4% of patients; ATM (4.4%), BRAF V600E (0.4%), BRCA1 (1.5%), BRCA2 (2.9%), ERBB2 amplification (9.2%), IDH1 (0.2%), KRAS G12C (0.7%), microsatellite instability-high (4.8%), NTRK1/2/3 fusion (0.13%), PIK3CA mutation (11.4%), and tumor mutational burden-high (9.4%). CDH1 alterations and MET amplification were significantly more frequent in patients aged < 40 years (27.7 and 6.2%) than in those aged ≥ 40 years (14.7 and 4.0%).
Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.
基于检测板的综合基因组分析在全球临床实践中均有应用；然而，晚期胃癌患者的大型真实世界数据集尚不为人熟知。
我们研究了分子定义或年龄分层亚组在临床相关改变方面存在哪些差异。
这是一项对来自综合基因组分析检测（Foundation Medicine公司）的真实世界数据集进行的合作生物标志物研究。对至少324个癌症相关基因以及31个在癌症中频繁重排的基因的选定内含子进行杂交捕获。总体而言，4634例患者可用于分析，并按年龄（≥40/<40岁）、微卫星不稳定性状态、肿瘤突变负荷状态（高≥10/低<10个突变/Mb）、爱泼斯坦-巴尔病毒状态以及选定的基因改变进行分层。我们采用校正了耶茨误差的卡方检验分析改变的频率。
频繁改变的基因包括TP53（60.1%）、ARID1A（19.6%）、CDKN2A（18.2%）、KRAS（16.6%）和CDH1（15.8%）。根据分子定义或年龄分层亚组观察到综合基因组分析存在差异。在31.4%的患者中检测到可靶向的基因组改变；ATM（4.4%）、BRAF V600E（0.4%）、BRCA1（1.5%）、BRCA2（2.9%）、ERBB2扩增（9.2%）、IDH1（0.2%）、KRAS G12C（0.7%）、微卫星高度不稳定（4.8%）、NTRK1/2/3融合（0.13%）、PIK3CA突变（11.4%）以及肿瘤突变负荷高（9.4%）。年龄<40岁的患者中CDH1改变和MET扩增显著比年龄≥40岁的患者更常见（分别为27.7%和6.2%比14.7%和4.0%）。
临床检测板检测的真实世界数据集揭示了胃癌按亚组划分的基因组格局。这些发现为当前胃癌治疗策略及未来治疗发展提供了见解。
