AIMS: The authors focused on a group of young lung cancer patients with the aim of better understanding the mechanisms of tumor pathogenesis in these patients and search for potential targetable mutations. METHODS: We collected retrospective data on patients under 40 years diagnosed with lung cancer (NSCLC or small-cell lung cancer) from 2011-2020 at the Department of Respiratory Diseases, University Hospital Brno, Czech Republic. Tumor tissue of these patients was analysed by next-generation sequencing (NGS, a panel of 550 variants in 19 genes). Demographic characteristics, smoking history, histology, molecular-genetic results and clinical stage of the disesase were recorded in all eligible patients from accessible medical databases. RESULTS: Of 17 identified patients in only 8 cases was successful NGS carried out due to lack of sufficient good quality material in the other cases. The most frequently found molecular genetic changes were EGFR, RICTOR and HER2 amplification and MET and FGFR1 amplification. In addition, we found rare pathogenic variants in BRAF and PIK3CA genes. Actionable variants were detected in 75% patients. CONCLUSION: We detected very frequent driver and potentially actionable alterations in young patients with lung cancer. This suggests different mechanisms of carcinogenesis in these patients and indicates that they might benefit more from a specific approach than older lung cancer patients.

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pathology University Hospital Brno Brno Czech Republic

Department of Respiratory Diseases University Hospital Brno Brno Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

International Clinical Research Center St Anne´s University Hospital Brno Czech Republic

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Bratova M, Karlinova B, Skrickova J, Pesek M, Kolek V, Koubkova L, Hrnciarik M, Krejci J, Barinova M, Havel L, Grygarkova I, Brat K. Non-small Cell Lung Cancer as a Chronic Disease - A Prospective Study from the Czech TULUNG Registry. In Vivo 2020;34(1):369-79. PubMed DOI

Cancer Incidence in the Czech Republic, The Institute of Health and Statistics of the Czech Republic, 2017. Avaliable from: https://www.uzis.cz/res/f/008318/novotvary2017.pdf, last accessed 8th February 2021.

Bigay-Gamé L, Bota S, Greillier L, Monnet I, Madroszyk A, Corre R, Mastroianni B, Falchero L, Mazières J, Colineaux H, Lepage B, Chouaid C; GFPC Investigators. Characteristics of Lung Cancer in Patients Younger than 40 Years: A Prospective Multicenter Analysis in France. Oncology 2018;95(6):337-43. PubMed DOI

Li F, He H, Qiu B, Ji Y, Sun K, Xue Q, Guo W, Wang D, Zhao J, Mao Y, Mu J, Gao S. Clinicopathological characteristics and prognosis of lung cancer in young patients aged 30 years and younger. J Thorac Dis 2019;11(10):4282-91. PubMed DOI

Galvez-Nino M, Ruiz R, Pinto JA, Roque K, Mantilla R, Raez LE, Mas L. Lung Cancer in the Young. Lung 2020;198(1):195-200. PubMed DOI

Vavalà T, Monica V, Lo Iacono M, Mele T, Busso S, Righi L, Papotti M, Scagliotti GV, Novello S. Precision medicine in age-specific non-small-cell-lung-cancer patients: Integrating biomolecular results into clinical practice-A new approach to improve personalized translational research. Lung Cancer 2017;107:84-90. PubMed DOI

Sacher AG, Dahlberg SE, Heng J, Mach S, Jänne PA, Oxnard GR. Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non-Small-Cell Lung Cancer. JAMA Oncol 2016;2(3):313-20. PubMed DOI

Yang S, Song Z, Cheng G. Genomic alterations and survival in young patients aged under 40 years with completely resected non-small cell lung cancer. Ann Transl Med 2019;7(7):140. PubMed DOI

Hou H, Zhu H, Zhao H, Yan W, Wang Y, Jiang M, Liu B, Liu D, Zhou N, Zhang C, Li P, Chang L, Guan Y, Wang Z, Zhang X, Li Z, Fang B, Zhang X. Comprehensive Molecular Characterization of Young Chinese Patients with Lung Adenocarcinoma Identified a Distinctive Genetic Profile. Oncologist 2018;23(9):1008-15. PubMed DOI

Chen Z, Teng X, Zhang J, Huang K, Shen Q, Cao H, Luo H, Yuan Y, Teng X. Molecular features of lung adenocarcinoma in young patients. BMC Cancer 2019;19(1):777. PubMed DOI

Luo W, Tian P, Wang Y, et al. Characteristics of genomic alterations of lung adenocarcinoma in young never-smokers. Int J Cancer 2018;143(7):1696-705. PubMed DOI

Bratova M, Brat K, Hurdalkova K, Barinova M, Drosslerova M, Kultan J, Wanke M, Koubkova L, Krejci J, Svaton M. Lung Cancer vs "Young Cancer" - Is Non-Small Cell Lung Cancer in Young Patient a Different Entity? J Adolesc Young Adult Oncol 2022;11(5):451-8. PubMed DOI

Guidelines for Predictive Testing of Solid Tumors, The Society of The Czech Pathologists, 2018. Avaliable from: http://www.patologie.info/standardy/35, last accessed 8th February 2021.

Slatko BE, Gardner AF, Ausubel FM. Overview of Next-Generation Sequencing Technologies. Curr Protoc Mol Biol 2018;122(1):e59. PubMed DOI

Behjati S, Tarpey PS. What is next generation sequencing? Arch Dis Child Educ Pract Ed 2013;98(6):236-8. PubMed DOI

Kozielski J, Kaczmarczyk G, Porębska I, Szmygin-Milanowska K, Gołecki M. Lung cancer in patients under the age of 40 years. Contemp Oncol 2012;16(5):413-5. PubMed DOI

Lara MS, Brunson A, Wun T, Tomlinson B, Qi L, Cress R, Gandara DR, Kelly K. Predictors of survival for younger patients less than 50 years of age with non-small cell lung cancer (NSCLC): a California Cancer Registry analysis. Lung Cancer 2014;85(2):264-9. PubMed DOI

Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: a brief review of recent epidemiological evidence. Lung Cancer 2004;45 Suppl 2:S3-9. PubMed DOI

Lee KW, Pausova Z. Cigarette smoking and DNA methylation. Front Genet 2013;4:132. PubMed DOI

Gao X, Zhang Y, Breitling LP, Brenner H. Tobacco smoking and methylation of genes related to lung cancer development. Oncotarget 2016;7(37):59017-28. PubMed DOI

Hirao T, Nelson HH, Ashok TD, Wain JC, Mark EJ, Christiani DC, Wiencke JK, Kelsey KT. Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer. Cancer Res 2001;61(2):612-5.

Chae YK, Davis AA, Agte S, Pan A, Simon NI, Iams WT, Cruz MR, Tamragouri K, Rhee K, Mohindra N, Villaflor V, Park W, Lopes G, Giles FJ. Clinical Implications of Circulating Tumor DNA Tumor Mutational Burden (ctDNA TMB) in Non-Small Cell Lung Cancer. Oncologist 2019;24(6):820-8. PubMed DOI

Kawaguchi T, Matsumura A, Fukai S, Tamura A, Saito R, Zell JA, Maruyama Y, Ziogas A, Kawahara M, Ignatius Ou SH. Japanese ethnicity compared with Caucasian ethnicity and never-smoking status are independent favorable prognostic factors for overall survival in non-small cell lung cancer: a collaborative epidemiologic study of the National Hospital Organization Study Group for Lung Cancer (NHSGLC) in Japan and a Southern California Regional Cancer Registry databases. J Thorac Oncol 2010;5(7):1001-10. PubMed DOI

D'Angelo SP, Pietanza MC, Johnson ML, Riely GJ, Miller VA, Sima CS, Zakowski MF, Rusch VW, Ladanyi M, Kris MG. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol 2011;29(15):2066-70. PubMed DOI

Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G, Yang PC. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014;9(2):154-62. PubMed DOI

Arrieta O, Cardona AF, Martín C, Más-López L, Corrales-Rodríguez L, Bramuglia G, Castillo-Fernandez O, Meyerson M, Amieva-Rivera E, Campos-Parra AD, Carranza H, Gómez de la Torre JC, Powazniak Y, Aldaco-Sarvide F, Vargas C, Trigo M, Magallanes-Maciel M, Otero J, Sánchez-Reyes R, Cuello M. Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J Thorac Oncol 2015;10(5):838-43. PubMed DOI

Dearden S, Stevens J, Wu YL, Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol 2013;24(9):2371-6. PubMed DOI

Scarpino S, Rampioni Vinciguerra GL, Di Napoli A, Fochetti F, Uccini S, Iacono D, Marchetti P, Ruco L. High prevalence of ALK+/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults. Lung Cancer 2016;97:95-8. PubMed DOI

Liu B, Quan X, Xu C, Lv J, Li C, Dong L, Liu M. Lung cancer in young adults aged 35 years or younger: A full-scale analysis and review. J Cancer 2019;10(15):3553-9. PubMed DOI

Xia J, Li H, Ji Y, Mi C, Chen G, Li P, Zhang R, Chen W, Wang J. Clinicopathologic characteristics and EGFR mutations in lung cancer patients aged below 45 years. Curr Probl Cancer 2019;43(4):363-70. PubMed DOI