AUTHOR=Liu Xia , Jiang Guopeng , Sun Xuefei , Su Guangfeng , Zhang Xuan , Shen Dan , Yan Na 

TITLE=Relationship between driver gene mutations and clinical pathological characteristics in older lung adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1275575

DOI=10.3389/fonc.2023.1275575

ISSN=2234-943X

ABSTRACT=<sec><title>Objectives</title><p>Lung adenocarcinoma (LUAD) is the most common newly diagnosed malignant tumor in older people. As older patients age, organ function decreases, leading to increased adverse reactions to treatment. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase tyrosine (ALK) tyrosine kinase inhibitors (TKIs) therapy are more effective and well-tolerated than chemotherapy, while the rate of genetic testing and subsequent targeted treatment among older patients remains relatively low, the clinical benefit limitation for those patients. This study aims to investigate the mutation characteristics of LUAD diver gene and its relationship with clinicopathological features in older LUAD.</p></sec><sec><title>Materials and methods</title><p>A total of 275 patients were diagnosed as LUAD and were over sixty years old. We utilized next-generation sequencing technology to detect and analyze gene mutations in postoperative tissue specimens, including <italic>EGFR, KRAS, ALK, ROS1, RET, MET, BRAF, HER2, PIK3CA</italic> and <italic>NRAS</italic>.</p></sec><sec><title>Results</title><p>A total of 90.18% (248/275) of older LUAD patients experienced genetic mutations. The <italic>EGFR</italic> (192, 69.82%) had the highest mutation rate among ten genes, followed by <italic>KRAS</italic> (21, 7.64%), <italic>MET</italic> (21, 7.64%), <italic>ERBB2</italic> (15, 5.45%), <italic>RET</italic> (9, 3.27%), <italic>ALK</italic> (8, 2.91%), <italic>ROS1</italic> (8, 2.91%), <italic>PIK3CA</italic> (6, 2.18%), <italic>BRAF</italic> (5, 1.82%) and <italic>NRAS</italic> (1, 0.36%). We also found thirty patients (15.63%) with <italic>EGFR</italic> mutations also having other gene mutations. The <italic>L858R</italic> mutation and exon19 deletion were the predominant <italic>EGFR</italic> mutations, accounting for 84.90% of <italic>EGFR</italic>-mutated patients. In addition, fifty-one kinds of <italic>EGFR</italic> mutations were detected, distributed in the protein tyrosine kinase catalytic domain (43, 84.31%), cysteine enriched domain (4, 7.84%), receptor binding domain (3, 5.88%), and EGFR transmembrane domain (1,1.96%). Ten cases of gene fusion mutation were detected. Two rare partner genes, <italic>PKHD1</italic> (P60:R34) and <italic>STK39</italic> (R33:S11), were detected by <italic>ROS1</italic> gene fusion. <italic>RET</italic> gene fusion revealed a rare companion gene <italic>KCND2</italic> (R11:K2). The <italic>EGFR</italic> mutations were more prevalent in female, non-smoking patients (p &lt; 0.05), and the <italic>KRAS</italic> mutations were more common in male and smoking patients (p &lt; 0.01). In addition, the <italic>BRAF</italic> mutations were more likely to occur in the right lung (p &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>Older LUAD populations exhibit diverse genetic mutations, which may also exist simultaneously. Simultaneous detection of multiple genes by NGS can accelerate and enhance targeted treatment benefits for older LUAD patients, ultimately improving their quality of life.</p></sec>