Kahraman-Cetin Nesibe, Akin Dilara, Orenay-Boyacioglu Seda, Boyacioglu Olcay, Erdogdu Ibrahim Halil, Oktay Esin, Meteoglu Ibrahim
Department of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiye.
Department of Medical Genetics, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiye.
Indian J Pathol Microbiol. 2024 Sep 14. doi: 10.4103/ijpm.ijpm_424_24.
The co-occurrence of lung adenocarcinoma and brain metastasis remains a significant cause of morbidity and mortality despite advancements in cancer treatment. The activity of neurofibromin, the product of Neurofibromatosis Type 1 gene (NF1), is crucial in regulating the RAS/MAPK pathway. The NF1 somatic mutations are significant in conditions such as melanoma, lung cancer, breast cancer, neuroblastoma, and central nervous system tumors.
Therefore, this research aims to uncover the profile of NF1 mutations and co-mutations in patients with brain metastases from lung adenocarcinoma, shedding light on their role in the pathophysiology of metastatic lung cancer.
In this study, a total of 131 (31 females, 90 males) patients diagnosed with metastatic lung adenocarcinoma who were examined in the Molecular Pathology Laboratory between 2019 and 2022 were retrospectively analyzed. The NF1 somatic mutations and co-mutations were evaluated using the NGS lung panel on the MiniSEQ NGS platform.
The average age of the 131 patients (31 females, 90 males) retrospectively examined in the study was 62.05 years. The ages of the cases included in the study followed a normal distribution according to Kolmogorov-Smirnov test (P = 0.200). Lymph node metastasis was detected in 48 patients (36.6%), while distant organ metastasis was observed in 81 patients (61.83%). Metastases were more frequently seen in males. No statistically significant difference was found between metastases and gender (P > 0.05). Distant organ metastasis (n = 26, 19.8%) and NF1 mutations (n = 8/26, 30.77%) were most commonly observed in the brain. The most common NF1 pathogenic variants in brain metastases were c.2325 + 3A > G (p.M1205fs*12) (n = 6/26, 23.07%) and c.1400C > T (p.T4671) (n = 5/26, 19.23%). There was no statistically significant relationship observed between patients' age, gender, brain metastasis, and NF1 mutation types (respectively, P = 0.98, P = 0.63, and P = 0.87). The mutations that showed the most association with NF1 mutations in brain metastases were PTEN and TP53.
Somatic NF1 mutations and co-mutations can play a critical driving force in metastatic lung adenocarcinoma and may contribute to treatment resistance. The mutational landscape of somatic NF1 mutations and co-mutations can provide new insights into the pathophysiology of metastatic lung cancer, especially those that have metastasized to the brain.
尽管癌症治疗取得了进展，但肺腺癌与脑转移同时发生仍是发病和死亡的重要原因。神经纤维瘤蛋白是1型神经纤维瘤病基因（NF1）的产物，其活性在调节RAS/MAPK通路中至关重要。NF1体细胞突变在黑色素瘤、肺癌、乳腺癌、神经母细胞瘤和中枢神经系统肿瘤等疾病中具有重要意义。
因此，本研究旨在揭示肺腺癌脑转移患者中NF1突变和共突变的情况，以阐明它们在转移性肺癌病理生理学中的作用。
本研究对2019年至2022年间在分子病理实验室接受检查的131例（31例女性，90例男性）诊断为转移性肺腺癌的患者进行了回顾性分析。使用MiniSEQ NGS平台上的NGS肺癌检测板评估NF1体细胞突变和共突变。
本研究回顾性检查的131例患者（31例女性，90例男性）的平均年龄为62.05岁。根据Kolmogorov-Smirnov检验，纳入研究的病例年龄呈正态分布（P = 0.200）。48例患者（36.6%）检测到淋巴结转移，81例患者（61.83%）观察到远处器官转移。转移在男性中更常见。转移与性别之间未发现统计学显著差异（P > 0.05）。远处器官转移（n = 26，19.8%）和NF1突变（n = 8/26，30.77%）最常见于脑。脑转移中最常见的NF1致病变体是c.2325 + 3A > G（p.M1205fs*12）（n = 6/26，23.07%）和c.1400C > T（p.T4671）（n = 5/26，19.23%）。患者的年龄、性别、脑转移和NF1突变类型之间未观察到统计学显著关系（分别为P = 0.98、P = 0.63和P = 0.87）。在脑转移中与NF1突变关联最密切的突变是PTEN和TP53。
体细胞NF1突变和共突变可能在转移性肺腺癌中发挥关键驱动力作用，并可能导致治疗耐药。体细胞NF1突变和共突变的突变图谱可为转移性肺癌的病理生理学提供新的见解，尤其是那些已转移至脑的患者。
