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CC BY 4.0 · Glob Med Genet 2024; 11(02): 175-186
DOI: 10.1055/s-0044-1787301
Original Article

Comparing Genomic Profiles of ALK Fusion-Positive and ALK Fusion-Negative Nonsmall Cell Lung Cancer Patients

Wenchao Xia
1   Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, People's Republic of China
,
Jing Yang
2   Department of Pathogenic Biology, Logistics University of Chinese People's Armed Police Force, Tianjin, People's Republic of China
,
Hongbin Li
3   Department of Oncology, Rongcheng County People's Hospital, Baoding, People's Republic of China
,
Ling Li
4   Department of Medicine, Yinfeng Gene Technology Co., Ltd., Jinan, People's Republic of China
,
Jinfeng Liu
5   Department of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
› Author Affiliations Funding None.
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Abstract

Background Anaplastic lymphoma kinase (ALK) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of ALK fusion-positive and ALK fusion-negative in a large cohort of NSCLC patients.

Methods The formalin-fixed paraffin-embedded specimens of NSCLC patients who underwent next-generation sequencing from 2020 to 2023 in Yinfeng Gene Technology Co., Ltd. Clinical laboratory were included in this study.

Results In the current study, a total of 180 (3.20%) patients tested positive for ALK fusions in 5,622 NSCLC samples. Within the ALK-positive cohort, a total of 228 ALK fusions were identified. Furthermore, five novel ALK fusion partners, including DAB1-ALK, KCMF1-ALK, KIF13A-ALK, LOC643770-ALK, and XDH-ALK were identified. In cases with ALK fusion-positive, TP53 alterations were the most prevalent (26.3%), followed by CDKN2A (8.4%), epidermal growth factor receptor (EGFR, 5.6%), and ALK (5.6%). By contrast, EGFR alterations were most prevalent (51%) in patients with ALK fusion-negative NSCLC, followed by TP53 (42.7%), KRAS (11.6%), and CDKN2A (11.3%). A total of 10 cases where ALK fusion co-occurred with EGFR mutations were also identified. Notably, the ALK fusion positivity rate was higher in younger patients (p < 0.0001) and in female patients (p = 0.0429). Additionally, positive ALK test results were more prevalent in patients with high programmed death-ligand 1 expression, especially when applying a 50% cutoff.

Conclusions Collectively, these findings offer valuable genomic insights that could inform the personalized clinical care of patients with NSCLC harboring ALK fusions within the context of precision medicine.

Keywords

NSCLC - ALK fusion - next-generation sequencing - genomic landscape

Author Contributions

W.X. collected and organized the data. J.Y. wrote the manuscript. H.L. prepared the figures. L.L. and J.L. critically revised the manuscript for intellectual content. All authors contributed to the article and approved the submitted version.


Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.




Publication History

Article published online:
13 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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