{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T18:14:54Z","timestamp":1783188894784,"version":"3.54.6"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,4]],"date-time":"2018-11-04T00:00:00Z","timestamp":1541289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572264, 81601994, 81330056, 81572253"],"award-info":[{"award-number":["81572264, 81601994, 81330056, 81572253"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,1,15]]},"abstract":"<jats:p><jats:italic>NF1<\/jats:italic> is a tumor suppressor gene that negatively regulates Ras signaling. <jats:italic>NF1<\/jats:italic> deficiency plays an important role in carcinogenesis. To investigate the frequency and clinical significance of <jats:italic>NF1<\/jats:italic> mutation, we examined mutation status of <jats:italic>NF1<\/jats:italic>, <jats:italic>TP53, LKB1<\/jats:italic> and <jats:italic>RB1<\/jats:italic> in 704 surgically resected lung adenocarcinomas from East Asian patients using semiconductor\u2010based Ion Torrent sequencing platform. Common driver events, including mutations in <jats:italic>EGFR<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>HER2<\/jats:italic>, <jats:italic>BRAF<\/jats:italic>, <jats:italic>MET,<\/jats:italic> and fusions affecting <jats:italic>ALK<\/jats:italic>, <jats:italic>RET<\/jats:italic> and <jats:italic>ROS1,<\/jats:italic> were also concurrently detected. The correlation between <jats:italic>NF1<\/jats:italic> mutations and clinicomolecular features of patients was further evaluated. Among 704 patients, 42 <jats:italic>NF1<\/jats:italic> mutations were found in 33 patients (33\/704, 4.7%), including 14 patients harboring <jats:italic>EGFR\/NF1<\/jats:italic> comutations (14\/33, 42.4%). Comparing with <jats:italic>EGFR<\/jats:italic>\u2010mutant patients, patients harboring <jats:italic>NF1<\/jats:italic> mutations were closely associated with solid component subtype (<jats:italic>p<\/jats:italic> = 0.028). Comparing with <jats:italic>KRAS<\/jats:italic> mutations, <jats:italic>NF1<\/jats:italic> mutations were found more common in female and never smokers (<jats:italic>p<\/jats:italic> = 0.003 and <jats:italic>p<\/jats:italic> = 0.004, respectively). Kaplan\u2013Meier survival analysis revealed that patients harboring <jats:italic>NF1<\/jats:italic> mutation had similar disease\u2010free survival (DFS) and overall survival (OS) with patients with <jats:italic>KRAS<\/jats:italic> mutation. Although frequently overlapped with <jats:italic>EGFR<\/jats:italic> mutation, patients harboring <jats:italic>NF1<\/jats:italic> mutation had significantly shorter DFS (<jats:italic>p<\/jats:italic> = 0.019) and OS (<jats:italic>p<\/jats:italic> = 0.004) than patients with <jats:italic>EGFR<\/jats:italic> mutation. During follow\u2010up, one female patient with <jats:italic>EGFR<\/jats:italic> exon 19 deletion and <jats:italic>NF1<\/jats:italic> Q1815X comutation showed poor response to EGFR TKIs (Gefitinib and Osimertinib) after disease relapse. In conclusion, <jats:italic>NF1<\/jats:italic> mutations define a unique molecular and clinicopathologic subtype of lung adenocarcinoma. Examination of <jats:italic>NF1<\/jats:italic> mutation may contribute to molecular subtyping and therapeutic intervention of lung adenocarcinoma.<\/jats:p>","DOI":"10.1002\/ijc.31871","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T14:05:59Z","timestamp":1537365959000},"page":"290-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Frequency and clinical significance of <i>NF1<\/i> mutation in lung adenocarcinomas from East Asian patients"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6117-8385","authenticated-orcid":false,"given":"Yunjian","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongze","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Difan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6802-096X","authenticated-orcid":false,"given":"Shanbo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Department of Pathology Fudan University Shanghai Cancer Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Department of Pathology Fudan University Shanghai Cancer Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihua","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7846-257X","authenticated-orcid":false,"given":"Haiquan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318206a221"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214886"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70184-X"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810699"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909530"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70364-X"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/351576a0"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90150-D"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010118"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603227"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2741\/3727"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20601"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-017-0109-3"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0741"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11404"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13385"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.08.029"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07423"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2377"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10937"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1890"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4592"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70489-8"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25546"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60578"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63193"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.6038"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.44.1477"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2014.02.007"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5549"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1616288"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2511"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028204"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep07163"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-015-5043-9"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.31871","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.31871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:36:02Z","timestamp":1694752562000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.31871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,4]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,1,15]]}},"alternative-id":["10.1002\/ijc.31871"],"URL":"https:\/\/doi.org\/10.1002\/ijc.31871","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,4]]},"assertion":[{"value":"2018-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}