Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma: Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim; Cancer Res Treat. 2024;56(1):104-114. Published online July 24, 2023; DOI: https://doi.org/10.4143/crt.2023.728

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Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

Citations

Citations to this article as recorded by

Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA
Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasu
Investigational New Drugs.2025;[Epub] CrossRef
A Novel CLTC::RPS6KB1 Fusion in a Poorly Differentiated Carcinoma Involving the Lung and Mediastinum
Mitchell Zhao, Nicholas Protopsaltis, Mina Sabet, Shulei Sun, Grace Lin, Farnaz Hasteh, Wei Song
International Journal of Surgical Pathology.2025;[Epub] CrossRef

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General

Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients: Yoon Jin Cha, Chung Lee, Bio Joo, Kyung A Kim, Choong-kun Lee, Hyo Sup Shim; Cancer Res Treat. 2023;55(4):1087-1095. Published online June 15, 2023; DOI: https://doi.org/10.4143/crt.2023.682

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Purpose
Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown.
Materials and Methods
We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed.
Results
Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions.
Conclusion
Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

Citations

Citations to this article as recorded by

Continuous multimodal data supply chain and expandable clinical decision support for oncology
Jee Suk Chang, Hyunwook Kim, Eun Sil Baek, Jeong Eun Choi, Joon Seok Lim, Jin Sung Kim, Sang Joon Shin
npj Digital Medicine.2025;[Epub] CrossRef
Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors
Chunwei Xu, Qian Wang, Dong Wang, Wenxian Wang, Wenfeng Fang, Ziming Li, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfen
Global Medical Genetics.2024; 11(01): 086. CrossRef
Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer
Hongyan Li, Lina Xu, Hongshun Cao, Tianyi Wang, Siwen Yang, Yixin Tong, Linlin Wang, Qiang Liu
Frontiers in Oncology.2024;[Epub] CrossRef
Analysis of CD74 Occurrence in Oncogenic Fusion Proteins
Jasmine Vargas, Georgios Pantouris
International Journal of Molecular Sciences.2023; 24(21): 15981. CrossRef

4,555 View
253 Download
4 Web of Science
4 Crossref

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