The NF1 gene mutations and co-mutations in lung adenocarcinomas with brain metastasis

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dc.contributor.authorKahraman-Cetin, Nesibeen_US
dc.contributor.authorAkin, Dilaraen_US
dc.contributor.authorOrenay-Boyacioglu, Sedaen_US
dc.contributor.authorBoyacioglu, Olcayen_US
dc.contributor.authorErdogdu, Ibrahim Halilen_US
dc.contributor.authorOktay, Esinen_US
dc.contributor.authorMeteoglu, Ibrahimen_US
dc.date.accessioned2025-08-13T11:40:49Z
dc.date.available2025-08-13T11:40:49Z
dc.date.issued2025-06
dc.description.abstractBackground: The co?occurrence of lung adenocarcinoma and brain metastasisremains a significant cause of morbidity and mortality despite advancements incancer treatment. The activity of neurofibromin, the product of NeurofibromatosisType 1 gene (NF1), is crucial in regulating the RAS/MAPK pathway. TheNF1 somatic mutations are significant in conditions such as melanoma, lungcancer, breast cancer, neuroblastoma, and central nervous system tumors.Objective: Therefore, this research aims to uncover the profile of NF1 mutationsand co-mutations in patients with brain metastases from lung adenocarcinoma,shedding light on their role in the pathophysiology of metastatic lung cancer.Materials and Methods: In this study, a total of 131 (31 females, 90 males)patients diagnosed with metastatic lung adenocarcinoma who were examined inthe Molecular Pathology Laboratory between 2019 and 2022 were retrospectivelyanalyzed. The NF1 somatic mutations and co-mutations were evaluated usingthe NGS lung panel on the MiniSEQ NGS platform. Results: The average ageof the 131 patients (31 females, 90 males) retrospectively examined in thestudy was 62.05 years. The ages of the cases included in the study followeda normal distribution according to Kolmogorov–Smirnov test (P = 0.200).Lymph node metastasis was detected in 48 patients (36.6%), while distantorgan metastasis was observed in 81 patients (61.83%). Metastases weremore frequently seen in males. No statistically significant difference was foundbetween metastases and gender (P > 0.05). Distant organ metastasis (n = 26,19.8%) and NF1 mutations (n = 8/26, 30.77%) were most commonly observedin the brain. The most common NF1 pathogenic variants in brain metastaseswere 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 relationshipobserved between patients’ age, gender, brain metastasis, and NF1 mutationtypes (respectively, P = 0.98, P = 0.63, and P = 0.87). The mutations that showedthe most association with NF1 mutations in brain metastases were PTEN andTP53. Conclusions: Somatic NF1 mutations and co-mutations can play acritical driving force in metastatic lung adenocarcinoma and may contribute totreatment resistance. The mutational landscape of somatic NF1 mutations andco-mutations can provide new insights into the pathophysiology of metastaticlung cancer, especially those that have metastasized to the brain.en_US
dc.identifier.affiliationsDepartment of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.affiliationsDepartment of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.affiliationsDepartment of Medical Genetics, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.affiliationsFaculty of Engineering, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.affiliationsDepartment of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiye; Department of Molecular Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.affiliationsDepartment of Oncology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.affiliationsDepartment of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Türkiyeen_US
dc.identifier.citationKahraman-Cetin Nesibe, Akin Dilara, Orenay-Boyacioglu Seda, Boyacioglu Olcay, Erdogdu Ibrahim Halil, Oktay Esin, Meteoglu Ibrahim. The NF1 gene mutations and co-mutations in lung adenocarcinomas with brain metastasis. Indian Journal of Pathology & Microbiology. 2025 Jun; 68(2): 294-299en_US
dc.identifier.issn0377-4929
dc.identifier.issn0974-5130
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/253968
dc.languageenen_US
dc.publisherWolters Kluwer - Medknowen_US
dc.relation.issuenumber2en_US
dc.relation.volume68en_US
dc.source.urihttps://doi.org/10.4103/ijpm.ijpm_424_24en_US
dc.subjectBrain metastasisen_US
dc.subjectcomutationen_US
dc.subjectlung adenocarcinomaen_US
dc.subjectneurofibromatosis type 1en_US
dc.subjectNF1 mutationsen_US
dc.titleThe NF1 gene mutations and co-mutations in lung adenocarcinomas with brain metastasisen_US
dc.typeJournal Articleen_US
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