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Genomic profiles of primary tumors (PT) and matched mediastinal lymph nodes (MLN) can uncover occult metastases, refine recurrence risk assessment, and support personalized treatment strategies in lung adenocarcinoma (LUAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>The study aimed to investigate clinically relevant somatic variants in formalin-fixed, paraffin-embedded (FFPE) PT and scrapings of MLN cytological slide samples using next-generation sequencing (NGS) and correlated the findings with overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>We retrospectively analyzed the genomic profile of PT and MLN from Brazilian LUAD patients between 2013 and 2020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Genomic DNA (gDNA) was extracted from PT and MLN matched samples of 32 patients (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200964). Targeted NGS was performed using the SureSelect XTHS2 panel. We analyzed OS using Kaplan\u2013Meier curves, and risk factors for mortality using univariate and multivariate Cox regression models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Clinically significant or potentially significant variants were identified in 72% of PT and 75% of MLN, totaling 46 and 51 variants, respectively. The most frequent variants in PT involved\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      (39.3%),\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      (28.6%),\n                      <jats:italic toggle=\"yes\">ATM<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                      (21.4% in both), whereas in MLN,\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      (35.7%),\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      (32.1%),\n                      <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      (14.3% in both), and\n                      <jats:italic toggle=\"yes\">ATM<\/jats:italic>\n                      (10.7%) have predominated. Co-mutations were detected in 31.3% of PT and 43.8% of MLN, with variant discordance between PT-MLN in 82.2% of cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Cox regression analysis demonstrated that the presence of co-mutations in MLN was a co-factor associated with poorer OS, while no significant associations were observed for PT variants. These findings highlight distinct genomic profiles between PT and MLN. Integrating the molecular profile of MLN into staging may improve prognostic accuracy and guide treatment decisions in LUAD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359251409007","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T04:47:48Z","timestamp":1769748468000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinically relevant somatic variants and genomic discordance between primary tumors and mediastinal lymph nodes in lung adenocarcinoma"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5272-2169","authenticated-orcid":false,"given":"Caroline Silv\u00e9rio","family":"Faria","sequence":"first","affiliation":[{"name":"Laboratorio de Investigacao Medica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Machado","family":"Baldavira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Histomorfometria e Genomica Pulmonar, Departamento de Patologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tabatha Gutierrez","family":"Prieto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Histomorfometria e Genomica Pulmonar, Departamento de Patologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilka Lopes","family":"Santoro","sequence":"additional","affiliation":[{"name":"Divisao Respiratoria, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane Rossi","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Instituto do Cancer do Estado de Sao Paulo, Servi\u00e7o de Cirurgia Tor\u00e1cica Oncol\u00f3gica, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen Caroline Toledo","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie Domenici","family":"Kulikowski","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigacao Medica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-2100","authenticated-orcid":false,"given":"Teresa Yae","family":"Takagaki","sequence":"additional","affiliation":[{"name":"Instituto do Coracao, Divisao de Pneumologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8146-5798","authenticated-orcid":false,"given":"Murilo","family":"Cervato","sequence":"additional","affiliation":[{"name":"ByMyCell, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Mingarini","family":"Terra","sequence":"additional","affiliation":[{"name":"Instituto do Cancer do Estado de Sao Paulo, Servi\u00e7o de Cirurgia Tor\u00e1cica Oncol\u00f3gica, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera Luiza","family":"Capelozzi","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Histomorfometria e Genomica Pulmonar, Departamento de Patologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Antonangelo","sequence":"additional","affiliation":[{"name":"Divisao de Patologia Clinica, Departamento de Patologia, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, Av. 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