Research Article
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In silico analysis of IL7RA missense mutations in lung, breast and skin cancers

Year 2025, Volume: 26 Issue: 1, 9 - 17, 15.04.2025

Zeynep Tokcaer Keskin

https://doi.org/10.23902/trkjnat.1545678

Abstract

Interleukin 7 (IL7)-Interleukin 7 Receptor Alpha (IL7RA) signaling is well investigated in hematological cancers, but in solid cancers, its role needs to be investigated further. In a recent study, IL7R was identified as a key gene in leptomeningeal carcinoma. Unfortunately, there is limited patient data on leptomeningeal carcinoma from breast, lung and skin cancers. In this study, IL7RA missense mutations that could have pathologic importance in lung, breast and skin cancers were analyzed in silico. Using Genomic Data Commons (GDC) data portal, lung, breast and melanoma data from 3250 patients were filtered to list IL7RA missense mutations. Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping v2 (PolyPhen2), Universal Mutation Database Predictor (UMD-Predictor) and Single Nucleotide Polymorphisms & Gene Ontology (E-SNP&GO) servers were employed to reveal pathogenic variants. Conservation Surface Mapping (ConSurf )was used to analyze conservation scores. Domains were investigated by InterPro tool. Molecular docking of IL7-IL7RA was performed by ClusPro, Mutational Binding free energy change predictor 2 (Mutabind2) and Protein-Ligand Interaction Profiler (PLIP) servers. Stability of the mutations were analyzed by Impact-Mutant 2.0 (I-Mutant2), Mutation Protein Stability Prediction (MUpro) and Impact of Non-synonymous mutations on Protein Stability-Multi Dimension (INPS-MD). Structural changes were determined using Dynamic Mutation predictor 2 (DynaMut2) and Have (y)Our Protein Explained (HOPE) servers. Out of 99 missense mutations identified, 6 (T56P, C57Y, K204I, S207F, G215V and W217C) were defined as pathogenic. All these mutations were primarily found in lung cancer and located in the extracellular domain of IL7RA. Although none were in the interaction interface of IL7, all were located at or next to conserved motifs. This proximity likely destabilizes IL7RA and drastically changes its bonding patterns. The IL7RA missense mutations may have a significant role in lung cancer, as they presumably change the protein’s function.

Keywords

Interlekin 7 Receptor Alpha missense mutation lung cancer computational biology in silico simulation

Ethical Statement

Since the article does not contain any studies with human or animal subject, its approval to the ethics committee was not required.

Supporting Institution

The author declared that this study has received no financial support.

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Year 2025, Volume: 26 Issue: 1, 9 - 17, 15.04.2025

Zeynep Tokcaer Keskin

https://doi.org/10.23902/trkjnat.1545678

Abstract

İnterlökin 7 (IL7)-İnterlökin 7 Reseptör Alfa (IL7RA) sinyali hematolojik kanserlerde iyi araştırılmış, ancak, solid kanserlerdeki rolünün daha fazla araştırılması gerekmektedir. Son yapılan bir çalışmada, IL7R leptomeningeal karsinomda anahtar gen olarak tanımlanmıştır. Meme, akciğer ve deri kanserlerinden kaynaklanan leptomeningeal karsinomda, ne yazık ki sınırlı sayıda hasta verisi bulunmaktadır. Bu çalışmada, akciğer, meme ve deri kanserlerinde patolojik öneme sahip olabilecek IL7RA yanlış anlamlı mutasyonları bilgisayarlı olarak analiz edildi. GDC veri portalı kullanılarak, 3250 hastadan alınan akciğer, meme ve deri kanseri verileri filtrelenerek IL7RA yanlış anlamlı mutasyonları listelendi. Patojenik varyantları ortaya çıkarmak için Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping v2 (PolyPhen2), Universal Mutation Database Predictor (UMD-Predictor)ve Single Nucleotide Polymorphisms & Gene Ontology (E-SNP&GO) sunucuları kullanıldı. Korunma puanları analiz etmek için Conservation Surface Mapping (ConSurf) kullanıldı. Domain adları InterPro aracıyla araştırıldı. IL7-IL7RA'nın moleküler yerleştirilmesi ClusPro, Mutational Binding free energy change predictor 2 (Mutabind2) ve Protein-Ligand Interaction Profiler (PLIP) sunucuları tarafından gerçekleştirildi. Mutasyonların stabilitesi Impact-Mutant 2.0 (I-Mutant2), Mutation Protein Stability Prediction (MUpro) ve Impact of Non-synonymous mutations on Protein Stability-Multi Dimension (INPS-MD) ile analiz edildi. Yapısal değişiklikler Dynamic Mutation predictor 2 (DynaMut2) ve Have (y)Our Protein Explained (HOPE) sunucuları kullanılarak belirlendi. Tanımlanan 99 yanlış anlamlı mutasyondan 6'sı (T56P, C57Y, K204I, S207F, G215V ve W217C) patojenik olarak belirlendi. Tüm mutasyonların öncelikli olarak akciğer kanserinde bulunduğu ve IL7RA'nın ekstraselüler alanında yerleştiği tespit edildi. Her ne kadar hiçbiri IL7 etkileşiminin ara yüzünde olmasa da, hepsi korunmuş motiflerin yanında veya yakınında konumlanmışlardı. Bu yakınlık IL7RA'yı istikrarsızlaştırmakta ve bağlanma paternini büyük ölçüde değiştirmektedir. IL7RA yanlış anlamlı mutasyonları muhtemelen proteinin işlevini değiştirdiği için akciğer kanserinde önemli bir role sahip olabilir.

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There are 45 citations in total.

Details

Primary Language English
Subjects Sequence Analysis, Receptors and Membrane Biology
Journal Section Research Article/Araştırma Makalesi
Authors

Zeynep Tokcaer Keskin 0000-0001-7678-0590

Early Pub Date February 11, 2025
Publication Date April 15, 2025
Submission Date September 9, 2024
Acceptance Date January 21, 2025
Published in Issue Year 2025 Volume: 26 Issue: 1

Cite

APA Tokcaer Keskin, Z. (2025). In silico analysis of IL7RA missense mutations in lung, breast and skin cancers. Trakya University Journal of Natural Sciences, 26(1), 9-17. https://doi.org/10.23902/trkjnat.1545678
AMA Tokcaer Keskin Z. In silico analysis of IL7RA missense mutations in lung, breast and skin cancers. Trakya Univ J Nat Sci. April 2025;26(1):9-17. doi:10.23902/trkjnat.1545678
Chicago Tokcaer Keskin, Zeynep. “In Silico Analysis of IL7RA Missense Mutations in Lung, Breast and Skin Cancers”. Trakya University Journal of Natural Sciences 26, no. 1 (April 2025): 9-17. https://doi.org/10.23902/trkjnat.1545678.
EndNote Tokcaer Keskin Z (April 1, 2025) In silico analysis of IL7RA missense mutations in lung, breast and skin cancers. Trakya University Journal of Natural Sciences 26 1 9–17.
IEEE Z. Tokcaer Keskin, “In silico analysis of IL7RA missense mutations in lung, breast and skin cancers”, Trakya Univ J Nat Sci, vol. 26, no. 1, pp. 9–17, 2025, doi: 10.23902/trkjnat.1545678.
ISNAD Tokcaer Keskin, Zeynep. “In Silico Analysis of IL7RA Missense Mutations in Lung, Breast and Skin Cancers”. Trakya University Journal of Natural Sciences 26/1 (April 2025), 9-17. https://doi.org/10.23902/trkjnat.1545678.
JAMA Tokcaer Keskin Z. In silico analysis of IL7RA missense mutations in lung, breast and skin cancers. Trakya Univ J Nat Sci. 2025;26:9–17.
MLA Tokcaer Keskin, Zeynep. “In Silico Analysis of IL7RA Missense Mutations in Lung, Breast and Skin Cancers”. Trakya University Journal of Natural Sciences, vol. 26, no. 1, 2025, pp. 9-17, doi:10.23902/trkjnat.1545678.
Vancouver Tokcaer Keskin Z. In silico analysis of IL7RA missense mutations in lung, breast and skin cancers. Trakya Univ J Nat Sci. 2025;26(1):9-17.

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