{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:23:56Z","timestamp":1787775836942,"version":"build-2784847793"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background:<\/jats:title>\n \n 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\n Neurofibromatosis Type 1 gene (NF1)<\/jats:italic>\n , is crucial in regulating the RAS\/MAPK pathway. The\n NF1<\/jats:italic>\n somatic mutations are significant in conditions such as melanoma, lung cancer, breast cancer, neuroblastoma, and central nervous system tumors.\n <\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n \n Therefore, this research aims to uncover the profile of\n NF1<\/jats:italic>\n mutations and co-mutations in patients with brain metastases from lung adenocarcinoma, shedding light on their role in the pathophysiology of metastatic lung cancer.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n 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\n NF1<\/jats:italic>\n somatic mutations and co-mutations were evaluated using the NGS lung panel on the MiniSEQ NGS platform.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n 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\u2013Smirnov test (\n P<\/jats:italic>\n = 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 (\n P<\/jats:italic>\n > 0.05). Distant organ metastasis (n = 26, 19.8%) and\n NF1<\/jats:italic>\n mutations (n = 8\/26, 30.77%) were most commonly observed in the brain. The most common\n NF1<\/jats:italic>\n 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\u2019 age, gender, brain metastasis, and\n NF1<\/jats:italic>\n mutation types (respectively,\n P<\/jats:italic>\n = 0.98,\n P<\/jats:italic>\n = 0.63, and\n P<\/jats:italic>\n = 0.87). The mutations that showed the most association with\n NF1<\/jats:italic>\n mutations in brain metastases were\n PTEN<\/jats:italic>\n and\n TP53<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Somatic\n NF1<\/jats:italic>\n 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\n NF1<\/jats:italic>\n mutations and co-mutations can provide new insights into the pathophysiology of metastatic lung cancer, especially those that have metastasized to the brain.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijpm.ijpm_424_24","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T13:21:52Z","timestamp":1726579312000},"page":"294-299","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["The NF1 gene mutations and co-mutations in lung adenocarcinomas with brain metastasis"],"prefix":"10.4103","volume":"68","author":[{"given":"Nesibe","family":"Kahraman-Cetin","sequence":"first","affiliation":[{"name":"Department of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, 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T\u00fcrkiye"},{"name":"Department of Molecular Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esin","family":"Oktay","sequence":"additional","affiliation":[{"name":"Department of Oncology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Meteoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Pathology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"R1-20250721","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung 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