{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:03Z","timestamp":1787028243020,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Genomic profiling guides treatment in metastatic non-small-cell lung cancer (mNSCLC), yet country-level data from T\u00fcrkiye remain limited. Methods: We retrospectively analyzed consecutive patients with mNSCLC diagnosed between January 2018 and March 2025 across tertiary centers in all seven regions. Variables included demographics, smoking, histology, testing modality (single-gene vs. next-generation sequencing [NGS]), targetable genomic alterations (TGAs) and co-mutations, and programmed death-ligand 1 (PD-L1) tumor proportion score. Results: Among 1023 patients (mean age 64 years; 76.4% male), tobacco exposure was frequent (mean 42.1 pack-years); 16.9% were never-smokers. NGS use increased over time, exceeding 90% by 2025. TGAs were detected in 28.3% (EGFR 16.0%, ALK 5.0%, KRAS G12C 2.6%, BRAF V600E 3.2%; ROS1, MET exon 14, HER2, NTRK \u2264 2.5%; no RET). EGFR alterations occurred in 19% of non-squamous carcinomas and 6% of squamous cell carcinomas (SCCs), suggesting an intermediate East\u2013West pattern. Among NGS-tested samples, TP53 was the most frequent co-mutation (33.1%), followed by alterations in CDKN2A, PIK3CA, FGFR, STK11, and KEAP1. Conclusions: In this large, multicenter Turkish real-world cohort, the TGA spectrum broadly mirrors global patterns while revealing local nuances; EGFR mutations were more frequent than expected in SCC, and nationwide NGS adoption is accelerating. Limitations include retrospective design, non-centralized PD-L1 testing, and missing data. Prospective, standardized studies integrating outcomes and resistance mechanisms are warranted to refine regional precision oncology.<\/jats:p>","DOI":"10.3390\/genes16121446","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T08:44:28Z","timestamp":1764751468000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bridging East and West: Real-World Clinicogenomic Landscape of Metastatic NSCLC in T\u00fcrkiye"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-3926","authenticated-orcid":false,"given":"K\u00fcbra","family":"Canaslan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dokuz Eylul University, Izmir 35330, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre","family":"Eken","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Atat\u00fcrk University, Erzurum 25240, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Bilici","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Atat\u00fcrk University, Erzurum 25240, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4124-3992","authenticated-orcid":false,"given":"Fahriye Merve","family":"Balc\u0131o\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya Research and Training Hospital, Antalya 07100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0290-8787","authenticated-orcid":false,"given":"Banu","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya Research and Training Hospital, Antalya 07100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"\u00c7akmak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-2646","authenticated-orcid":false,"given":"\u00d6znur","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-4927","authenticated-orcid":false,"given":"G\u00f6rkem","family":"Turhan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Karadeniz Technical University, Trabzon 61080, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feyyaz","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Karadeniz Technical University, Trabzon 61080, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-5567","authenticated-orcid":false,"given":"Hayati","family":"Arvas","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dicle University, Diyarbak\u0131r 21280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhat","family":"Urak\u00e7\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dicle University, Diyarbak\u0131r 21280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"\u00c7i\u00e7ek","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u0130stanbul University Cerrahpa\u015fa, Istanbul 34320, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep Hande","family":"Turna","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u0130stanbul University Cerrahpa\u015fa, Istanbul 34320, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Karao\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dokuz Eylul University, Izmir 35330, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cancergen.2024.06.002","article-title":"Cancer treatments: Past, present, and future","volume":"286\u2013287","author":"Sonkin","year":"2024","journal-title":"Cancer Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.21037\/atm-22-4444","article-title":"Developments in targeted therapy & immunotherapy-how non-small cell lung cancer management will change in the next decade: A narrative review","volume":"11","author":"Li","year":"2023","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"354","DOI":"10.6004\/jnccn.2025.0043","article-title":"NCCN Guidelines\u00ae Insights: Non-Small Cell Lung Cancer, Version 7.2025","volume":"23","author":"Riely","year":"2025","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.5858\/arpa.2017-0388-CP","article-title":"Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology","volume":"142","author":"Lindeman","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.jtho.2022.06.001","article-title":"Lung Cancer in Turkey","volume":"17","author":"Yumuk","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_6","unstructured":"(2025, August 04). Turkish Statistical Institute, Available online: https:\/\/data.tuik.gov.tr\/Kategori\/GetKategori?p=Nufus-ve-Demografi-109."},{"key":"ref_7","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_8","unstructured":"(2025, August 05). GATS (Global Adult Tobacco Survey) Fact Sheet, Turkey 2016. Available online: https:\/\/extranet.who.int\/ncdsmicrodata\/index.php\/catalog\/872."},{"key":"ref_9","first-page":"145","article-title":"The effect of HOTAIR gene variants on the development of bladder cancer and its clinicopathological characteristics in a Caucasian population","volume":"296\u2013297","author":"Sulhan","year":"2025","journal-title":"Cancer Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e6852","DOI":"10.1002\/cam4.6852","article-title":"Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients","volume":"13","author":"Agaoglu","year":"2024","journal-title":"Cancer Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.annonc.2022.12.009","article-title":"Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Hendriks","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_12","unstructured":"(2025, August 04). Social Security Institution, Available online: https:\/\/www.sgk.gov.tr\/Istatistik\/Yillik\/fcd5e59b-6af9-4d90-a451-ee7500eb1cb4\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4274\/balkanmedj.2017.0297","article-title":"Prevalence of Epidermal Growth Factor Receptor Mutations in Patients with Non-Small Cell Lung Cancer in Turkish Population","volume":"34","author":"Tezel","year":"2017","journal-title":"Balk. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Calibasi-Kocal, G., Amirfallah, A., Sever, T., Umit Unal, O., Gurel, D., Oztop, I., Ellidokuz, H., and Basbinar, Y. (2020). EGFR mutation status in a series of Turkish non-small cell lung cancer patients. Biomed. Rep., 13.","DOI":"10.3892\/br.2020.1308"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s40291-021-00563-1","article-title":"Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis","volume":"26","author":"Melosky","year":"2022","journal-title":"Mol. Diagn. Ther."},{"key":"ref_16","first-page":"108","article-title":"The prevalence of EGFR mutations in non-small cell lung cancer in an unselected Caucasian population","volume":"123","author":"Skov","year":"2015","journal-title":"J. Pathol. Microbiol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1038\/bjc.2013.511","article-title":"EGFR mutational status in a large series of Caucasian European NSCLC patients: Data from daily practice","volume":"109","author":"Gahr","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Zhu, L., and Zhang, J. (2015). Epidermal growth factor receptor gene mutation status in pure squamous-cell lung cancer in Chinese patients. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1056-9"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S253","DOI":"10.1016\/j.annonc.2020.08.181","article-title":"29P Genomic features of Chinese lung squamous cell carcinoma patients","volume":"31","author":"Zhao","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.lungcan.2017.08.021","article-title":"EGFR mutation prevalence in Asia-Pacific and Russian patients with advanced NSCLC of adenocarcinoma and non-adenocarcinoma histology: The IGNITE study","volume":"113","author":"Han","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.jtho.2021.11.003","article-title":"The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015","volume":"17","author":"Nicholson","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_22","first-page":"102","article-title":"The Epidermal Growth Factor, Anaplastic Lymphoma Kinase, and ROS Proto-oncogene 1 Mutation Profile of Non-Small Cell Lung Carcinomas in the Turkish Population: A Single-Center Analysis","volume":"25","year":"2024","journal-title":"Thorac. Res. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4274\/hamidiyemedj.galenos.2020.74429","article-title":"Oncogenic Mutation Frequencies in Lung Cancer Patients","volume":"1","author":"Ayten","year":"2020","journal-title":"Hamidiye Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103929","DOI":"10.1016\/j.critrevonc.2023.103929","article-title":"Meta-analysis of the prognostic impact of TP53 co-mutations in EGFR-mutant advanced non-small-cell lung cancer treated with tyrosine kinase inhibitors","volume":"184","author":"Ferrara","year":"2023","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Qin, K., Hou, H., Liang, Y., and Zhang, X. (2020). Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: A meta-analysis. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06805-5"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107249","DOI":"10.1016\/j.lungcan.2023.107249","article-title":"The significance of co-mutations in EGFR-mutated non-small cell lung cancer: Optimizing the efficacy of targeted therapies?","volume":"181","author":"Pezzuto","year":"2023","journal-title":"Lung Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jtho.2021.10.013","article-title":"Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status","volume":"17","author":"Ricciuti","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1158\/2159-8290.CD-18-0099","article-title":"STK11\/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma","volume":"8","author":"Skoulidis","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lungcan.2017.12.003","article-title":"PD-L1 expression according to the EGFR status in primary lung adenocarcinoma","volume":"116","author":"Takada","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/annonc\/mdz141","article-title":"EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer","volume":"30","author":"Hastings","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_31","first-page":"100187","article-title":"Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers","volume":"2","author":"Choudhury","year":"2021","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1093\/annonc\/mdy263","article-title":"A framework to rank genomic alterations as targets for cancer precision medicine: The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)","volume":"29","author":"Mateo","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cancergen.2025.07.006","article-title":"Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach","volume":"296\u2013297","author":"Kim","year":"2025","journal-title":"Cancer Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e012288","DOI":"10.1136\/jitc-2025-012288","article-title":"Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: The role of KEAP1, SMARCA4, and PTEN mutations","volume":"13","author":"Paredes","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_35","first-page":"105","article-title":"Overview of perspectives on cancer, newer therapies, and future directions","volume":"10","author":"Joshi","year":"2024","journal-title":"Oncol. Transl. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/12\/1446\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T08:53:03Z","timestamp":1764751983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/12\/1446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["genes16121446"],"URL":"https:\/\/doi.org\/10.3390\/genes16121446","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,3]]}}}