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中国肺腺癌的基因改变图谱及其对靶向治疗疗效的影响

Genetic Alteration Profiling of Chinese Lung Adenocarcinoma and Its Effect on Targeted Therapy Efficacy.

作者信息

Liu Jie, Xu Wang-Yang, Ye Maosong, Liu Zilong, Li Chun

机构信息

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Medicine, Singlera Genomics (Shanghai) Ltd., Shanghai, China.

出版信息

Front Oncol. 2021 Dec 14;11:726547. doi: 10.3389/fonc.2021.726547. eCollection 2021.

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a highly heterogeneous disease with a diversity of phenotypes and genotypes in different populations. The purpose of this study is to investigate oncogenic alterations of lung adenocarcinoma (LUAD) in eastern China and their significance in targeted therapies.

METHODS

This study enrolled 101 LUAD patients and used a customized DNA panel to detect molecular alterations. Comprehensive analysis of mutations and clinical application of genomic profiling was carried out.

RESULTS

The most commonly mutated genes were epidermal growth factor receptor () (53%) and tumor protein p53 () (32%). The less frequently mutated genes were erb-b2 receptor tyrosine kinase 2 () (25%), ATR serine/threonine kinase () (20%), CCAAT enhancer binding protein alpha () (16%), RB transcriptional corepressor 1 () (16%), transcription factor 7 like 2 () (14%), ROS proto-oncogene 1, receptor tyrosine kinase () (12%) and spectrin alpha, erythrocytic 1 () (12%). Among them, the frequency of , , , and mutations was much higher than that in the databases. Seventy percent of the patients harbored at least one actionable alteration according to the OncoKB evidence. mutations affected the efficacy of -tyrosine kinase inhibitors. , and mutated tumors tend to have higher tumor mutation burden (TMB).

CONCLUSIONS

LUAD patients from eastern China have a unique profile of mutations. The targeted DNA panel is helpful for personalized treatment decision of LUAD patients, and specific mutations may affect the efficacy of targeted therapies.

摘要

背景

非小细胞肺癌(NSCLC)是最常见的肺癌类型,是一种高度异质性疾病,在不同人群中具有多种表型和基因型。本研究的目的是调查中国东部肺腺癌(LUAD)的致癌改变及其在靶向治疗中的意义。

方法

本研究纳入了101例LUAD患者,并使用定制的DNA检测板检测分子改变。对突变进行了综合分析,并开展了基因组分析的临床应用。

结果

最常发生突变的基因是表皮生长因子受体(EGFR)(53%)和肿瘤蛋白p53(TP53)(32%)。较少发生突变的基因是erb-b2受体酪氨酸激酶2(ERBB2)(25%)、ATR丝氨酸/苏氨酸激酶(ATR)(20%)、CCAAT增强子结合蛋白α(CEBPA)(16%)、RB转录共抑制因子1(RB1)(16%)、转录因子7样2(TCF7L2)(14%)、ROS原癌基因1、受体酪氨酸激酶(ROS1)(12%)和血影蛋白α、红细胞1(SPTA1)(12%)。其中,EGFR、TP53、ERBB2、RB1和ROS1突变的频率远高于数据库中的频率。根据OncoKB证据,70%的患者至少有一个可靶向治疗的改变。EGFR突变影响EGFR-酪氨酸激酶抑制剂的疗效。RB1、TP53和CEBPA突变的肿瘤往往具有更高的肿瘤突变负荷(TMB)。

结论

中国东部的LUAD患者具有独特的突变谱。靶向DNA检测板有助于LUAD患者的个性化治疗决策,特定突变可能影响靶向治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6761/8712938/a084b353cf4e/fonc-11-726547-g001.jpg

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