Landscape of Concomitant Driver Alterations in Classical <i>EGFR</i>-Mutated Non–Small Cell Lung Cancer-Reference-Cited by-同舟云学术

Landscape of Concomitant Driver Alterations in Classical EGFR-Mutated Non–Small Cell Lung Cancer

Published:2024-08 Issue:8 Volume: Page:
ISSN:2473-4284
Container-title:JCO Precision Oncology
language:en
Short-container-title:JCO Precis Oncol

Author:

Wang Huaying¹,Lin Lie²^ORCID,Liang Chuqiao³^ORCID,Pang Jiaohui³,Yin Jiani C.³,Zhang Junli³,Shao Yang³⁴,Sun Chengming⁵,Guo Renhua⁶^ORCID

Affiliation:

1. Department of Respiratory and Critical Care Medicine, The Affiliated People's Hospital of Ningbo University, Ningbo Yinzhou People's Hospital, Ningbo, Zhejiang, China

2. Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China

3. Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, Jiangsu, China

4. School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

5. Department of Clinical Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China

6. Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Abstract

PURPOSE Next-generation sequencing (NGS) has enabled the detection of concomitant driver alterations in non–small cell lung cancer (NSCLC). However, the magnitude and clinical relevance of concomitant drivers remain to be explored. METHODS We profiled concomitant driver alterations of EGFR+ NSCLC by using targeted NGS. The associated genomic and clinical features were analyzed and validated in an independent The Cancer Genome Atlas cohort of patients with EGFR+ NSCLC. RESULTS Out of the total patient population, 334 patients had EGFR mutations along with concomitant driver mutations, comprising 3.09% of the entire cohort. The most frequent co-occurring mutations with sensitizing EGFR mutations include KRAS at 53.9%, followed by ERBB2 at 24.3%, MET at 16.5%, and BRAF at 3.3%. KRAS mutations in concomitant drivers were frequently hyperexchange mutations (25.6% v 8.2%, P < .001), compared with KRAS single drivers. EGFR/ ERBB2 drivers exhibited a higher incidence of ERBB2 amplification (40.7% v 16.5%, P < .001) and p.S310F/Y mutations (44.4% v 4.3%, P < .001) compared with ERBB2 alone. EGFR/ MET drivers had a higher frequency of MET amplification (71.4% v 43.3%) than MET single drivers. At the genomic level, the median number of additional concurrent mutations was four, with TSC2 (4%), CD274 (1%), and TP53 (63%) being the most frequently coaltered genes in concomitant driver tumors. Interestingly, clonality analysis indicated that EGFR mutations were more likely to occur as clonal events, whereas the codrivers were more often subclonal. Patients with concomitant drivers or with concomitant MET amplification exhibited worse prognosis. CONCLUSION These findings might aid in the selection of effective therapeutic regimens and facilitate the development of combination therapies.

Publisher

American Society of Clinical Oncology (ASCO)

Link

https://ascopubs.org/doi/pdfdirect/10.1200/PO.23.00520

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