Higher TP53 somatic mutation prevalence from liquid biopsy analysis in ever smoker non-small-cell lung cancer patients.

Autor:	Erdem HB; Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Türkiye; University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Medical Genetics, Ankara, Türkiye. Electronic address: haktanbagis.erdem@sbu.edu.tr., Alay MT; Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Türkiye., Özdemir Z; Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Türkiye., Çevik E; Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Türkiye., Ateş Ö; University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Medical Oncology, Ankara, Türkiye., Karaçin C; University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Medical Oncology, Ankara, Türkiye., Şahin İ; Arabian Gulf University Medical Faculty, Department of Medical Genetics, Manama, Bahrain., Doğan M; University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Medical Oncology, Ankara, Türkiye., Bahsi T; Ankara Etlik City Hospital, Department of Medical Genetics, Ankara, Türkiye.
Jazyk:	angličtina
Zdroj:	Mutation research [Mutat Res] 2024 Jan-Jun; Vol. 828, pp. 111847. Date of Electronic Publication: 2023 Nov 28.
DOI:	10.1016/j.mrfmmm.2023.111847
Abstrakt:	Objective: Cigarette smoking is a primary risk factor, linked to 80% of LC deaths. TP53, a key gene, is implicated in various cancers, with TP53 alterations in 36.7% of cancers. This research aims to investigate TP53 mutations detected in NSCLC patients by liquid biopsy and explore the relationship between these mutations and smoking history. Material and Method: The study enrolled a total of 340 patients diagnosed with non-small cell lung cancer (NSCLC). For sequencing, the Illumina NextSeq 500 system was utilized. The oncogenicity of the variants was assessed according to the ClinGen/CGC/VICC SOP and the variants were categorized into four tiers according to AMP/ASCO/CAP. Results: The most common mutations were in TP53 (48.7%), followed by EGFR, PIK3CA, and PTEN. Missense mutations were frequent, with TP53 and EGFR having higher rates in ever-smokers. No indels or complex mutations were found in ever-smokers. Patient age ranged from 20 to 86 years. Tier I-II variants were more common in ever-smokers, while Tier III variants were prevalent in never-smokers. TP53 mutations were more frequent in ever-smokers, showing a strong association with smoking. Domain distribution showed differences in PIK3CA. Transversion/transition ratios varied by gene and smoking status. Discussion: The presence of TP53 mutations is strongly associated with both cigarette smoking and elevated Tv/Ti ratios. The tier status of TP53, EGFR, and PTEN variants does not show a specific domain distribution, but interesting associations are observed between the tier status and domain distribution in PIK3CA variants. Therefore, further comprehensive investigations are needed to explore this entity, as well as the underlying factors contributing to the increased Tv/Ti rates in the TP53 gene. Such research will provide deeper insights into the genetic alterations associated with smoking and tumor heterogeneity, ultimately aiding in the development of targeted therapies. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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