Genomic analysis of comprehensive next generation sequencing data to explore the criteria for MET amplification as an actionable biomarker in NSCLC.

IF 4.5 2区 医学 Q1 ONCOLOGY Lung Cancer Pub Date : 2025-01-04 DOI:10.1016/j.lungcan.2025.108081
David Chun Cheong Tsui, Jessica K Lee, Candice Francheska B Tambaoan, Jason Hughes, Bernard Fendler, Brennan Decker, Garrett M Frampton, Alexa B Schrock, D Ross Camidge
{"title":"Genomic analysis of comprehensive next generation sequencing data to explore the criteria for MET amplification as an actionable biomarker in NSCLC.","authors":"David Chun Cheong Tsui, Jessica K Lee, Candice Francheska B Tambaoan, Jason Hughes, Bernard Fendler, Brennan Decker, Garrett M Frampton, Alexa B Schrock, D Ross Camidge","doi":"10.1016/j.lungcan.2025.108081","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>MET amplification (METamp) can be a de novo or acquired resistance driver; however, the definition of METamp that best captures patients who may respond to targeted therapy remains debated. We explored the genomic landscape of METamp NSCLC including degree of amplification, co-drivers, amplicon size, and outcomes to MET inhibitors.</p><p><strong>Methods: </strong>Hybrid-capture NGS-based genomic profiling from 88,547 tissue and 12,428 liquid NSCLC samples were queried for METamp (copy number (CN) ≥ ploidy + 4, or amplification ratio (AmpRatio; [CN/sample ploidy] ≥ 3). A nationwide de-identified real-world (rw) clinico-genomic database (CGDB) of NGS results linked to deidentified, electronic health record-derived clinical data was used to assess treatment and outcomes.</p><p><strong>Results: </strong>Among 10,760 evaluable patients in CGDB, 362 (3.4%) had a METamp. In targeted therapy-naïve cases, MET AmpRatio negatively correlated with non-METex14 co-drivers (median 4.1 vs 2.9, p < 0.0001). MET AmpRatio was not significantly correlated with tumor mutational burden (p = 0.79) but was inversely correlated with amplicon size (p < 0.001). Among paired METamp tissue samples, 8/30 had METamp detected in liquid; higher tumor fraction and AmpRatio were associated with liquid detection. Among 39 METamp patients receiving MET inhibitors, longer median real-world progression free survival was observed with MET AmpRatio ≥ 3 vs < 3 (4.9 vs. 1.7mos, HR 0.53 [95 %CI:0.21-1.3]).</p><p><strong>Conclusions: </strong>MET AmpRatio positively correlated with focal amplification and absence of co-drivers and trended with increased benefit from MET inhibitors. Further studies evaluatingcombinatorial data including MET AmpRatio, amplicon size and presence of other potential drivers, as predictive biomarkers for therapies targeting MET amplification in NSCLC are warranted.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108081"},"PeriodicalIF":4.5000,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lung Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.lungcan.2025.108081","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: MET amplification (METamp) can be a de novo or acquired resistance driver; however, the definition of METamp that best captures patients who may respond to targeted therapy remains debated. We explored the genomic landscape of METamp NSCLC including degree of amplification, co-drivers, amplicon size, and outcomes to MET inhibitors.

Methods: Hybrid-capture NGS-based genomic profiling from 88,547 tissue and 12,428 liquid NSCLC samples were queried for METamp (copy number (CN) ≥ ploidy + 4, or amplification ratio (AmpRatio; [CN/sample ploidy] ≥ 3). A nationwide de-identified real-world (rw) clinico-genomic database (CGDB) of NGS results linked to deidentified, electronic health record-derived clinical data was used to assess treatment and outcomes.

Results: Among 10,760 evaluable patients in CGDB, 362 (3.4%) had a METamp. In targeted therapy-naïve cases, MET AmpRatio negatively correlated with non-METex14 co-drivers (median 4.1 vs 2.9, p < 0.0001). MET AmpRatio was not significantly correlated with tumor mutational burden (p = 0.79) but was inversely correlated with amplicon size (p < 0.001). Among paired METamp tissue samples, 8/30 had METamp detected in liquid; higher tumor fraction and AmpRatio were associated with liquid detection. Among 39 METamp patients receiving MET inhibitors, longer median real-world progression free survival was observed with MET AmpRatio ≥ 3 vs < 3 (4.9 vs. 1.7mos, HR 0.53 [95 %CI:0.21-1.3]).

Conclusions: MET AmpRatio positively correlated with focal amplification and absence of co-drivers and trended with increased benefit from MET inhibitors. Further studies evaluatingcombinatorial data including MET AmpRatio, amplicon size and presence of other potential drivers, as predictive biomarkers for therapies targeting MET amplification in NSCLC are warranted.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
全面的下一代测序数据的基因组分析,探索MET扩增作为非小细胞肺癌可操作的生物标志物的标准。
简介:MET放大器(METamp)可以是一个新的或获得电阻驱动器;然而,METamp的定义仍然存在争议,该定义最好地捕获了可能对靶向治疗有反应的患者。我们探索了METamp NSCLC的基因组景观,包括扩增程度、共同驱动因素、扩增子大小和MET抑制剂的结果。方法:从88,547例组织和12,428例NSCLC液体样本中查询基于混合捕获ngs的基因组图谱,检测METamp(拷贝数(CN)≥倍体+ 4,或扩增比(AmpRatio;[cn /样本倍性]≥3)。NGS结果的全国去识别现实世界(rw)临床基因组数据库(CGDB)与去识别的电子健康记录衍生临床数据相关联,用于评估治疗和结果。结果:在10760例可评估的CGDB患者中,362例(3.4%)有METamp。在靶向therapy-naïve病例中,MET AmpRatio与非metex14共同驱动因素呈负相关(中位数为4.1 vs 2.9, p)。结论:MET AmpRatio与病灶放大和缺乏共同驱动因素呈正相关,并且MET抑制剂的获益增加。进一步的研究评估组合数据,包括MET扩增比、扩增子大小和其他潜在驱动因素的存在,作为非小细胞肺癌MET扩增治疗的预测性生物标志物是有必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Lung Cancer
Lung Cancer 医学-呼吸系统
CiteScore
9.40
自引率
3.80%
发文量
407
审稿时长
25 days
期刊介绍: Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.
期刊最新文献
Association of single nucleotide polymorphisms rs7459185 of the HSPβ1 gene and the risk of hematological toxicity in lung cancer. Clinical utility of comprehensive genomic profiling in non-small cell lung cancer: An analysis of a nation-wide database. Rearranged during transfection (RET) lung cancer - Update on targeted therapies. Targeted therapy for older patients with an oncogene driven non-small cell lung cancer: Recommendations from a SIOG expert group. Validation of the 9th edition of the TNM staging system for limited-stage small cell lung cancer after Resection: A multicenter study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1