Genomic Landscape and Tumor Mutational Burden Determination of Circulating Tumor DNA in Over 5,000 Chinese Patients with Lung Cancer

肺癌 循环肿瘤DNA 医学 癌症 DNA 癌症研究 生物 病理 遗传学
作者
Jie Shi,Zhiyu Wang,Junping Zhang,Yaping Xu,Xiao Xiao,Xiangming Quan,Ying Bai,Xia Yang,Zongjuan Ming,Xiaojin Guo,Huijing Feng,Xiaoling Yang,Xiaofei Zhuang,Fei Han,Kai Wang,Yonglei Shi,Yu Lei,Jun Bai,Shuanying Yang
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:27 (22): 6184-6196 被引量:13
标识
DOI:10.1158/1078-0432.ccr-21-1537
摘要

Abstract Purpose: Having emerged as a noninvasive and clinically applicable approach for molecular determination of lung cancer, a genomic overview of circulating tumor DNA (ctDNA) of large-scale cohort may be helpful in novel biomarker development and therapeutic innovation. Experimental Design: Primary cohort encompasses 5,671 blood samples from 4,892 patients with lung cancer. Pair-wise tissue samples from 579 patients and additional 358 sample pairs were collected to evaluate the correlation between blood and tissue tumor mutational burden (TMB). Parallel sequencing with plasma/tissue and white blood cells was performed using a 1,021-gene panel. Results: Histologic subtyping was the most relevant to ctDNA detectability independent of other demographic characteristics, with small cell lung cancer showing the highest detectability, ctDNA abundance, and blood TMB (bTMB). Mutational landscape demonstrated significant differences, and integrated clonality analysis highlighted distinct driver-pattern and functional pathway interaction among various subtypes. The clonality and concurrent genes of EGFR mutations could predict the therapeutic efficacy of tyrosine kinase inhibitors (TKI), and RB1 mutations in non–small cell lung cancer characterized a subset with high bTMB, elevated ctDNA level, and potential small cell transformation. Most importantly, we developed an adjusted algorithm for bTMB in samples with extremely low ctDNA level and validated its correlation with tissue TMB in an independent cohort. Conclusions: ctDNA could serve as a promising alternative in genomic profiling for lung cancer. The novel identification of ctDNA clonality and adjusted bTMB might improve therapeutic and prognostic evaluation. This dataset was also a valuable resource for the development of new therapeutic targets and new genomically guided clinical trials.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
nagi发布了新的文献求助10
2秒前
jfeng完成签到,获得积分10
4秒前
JN完成签到,获得积分10
12秒前
忐忑的书桃完成签到 ,获得积分10
13秒前
qaplay完成签到 ,获得积分0
13秒前
友好语风完成签到,获得积分10
14秒前
CLTTTt完成签到,获得积分10
15秒前
yk完成签到,获得积分10
17秒前
甜美的初蓝完成签到 ,获得积分10
21秒前
早安完成签到 ,获得积分10
25秒前
初昀杭完成签到 ,获得积分10
29秒前
量子星尘发布了新的文献求助10
31秒前
LIU完成签到 ,获得积分10
31秒前
33秒前
nianshu完成签到 ,获得积分0
34秒前
starwan完成签到 ,获得积分10
35秒前
松松发布了新的文献求助20
35秒前
hooddy123459发布了新的文献求助10
36秒前
wenhuanwenxian完成签到 ,获得积分10
40秒前
happy完成签到 ,获得积分10
44秒前
拾壹完成签到,获得积分10
52秒前
雪花完成签到,获得积分10
54秒前
清风完成签到 ,获得积分10
54秒前
雪花发布了新的文献求助10
58秒前
秀丽笑容完成签到 ,获得积分10
1分钟前
江湖应助聪慧芷巧采纳,获得10
1分钟前
量子星尘发布了新的文献求助10
1分钟前
Rjy完成签到 ,获得积分10
1分钟前
性感母蟑螂完成签到 ,获得积分10
1分钟前
ruochenzu完成签到,获得积分10
1分钟前
陈尹蓝完成签到 ,获得积分10
1分钟前
天道酬勤完成签到,获得积分10
1分钟前
1分钟前
仁爱的谷南完成签到,获得积分10
1分钟前
雯雯完成签到 ,获得积分10
1分钟前
一路有你完成签到 ,获得积分10
1分钟前
1分钟前
ruochenzu发布了新的文献求助10
1分钟前
1分钟前
wanghao完成签到 ,获得积分10
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022