Molecular and In Silico Analysis of the CHEK2 Gene in Individuals with High Risk of Cancer Predisposition from Turkiye

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dc.authorid0009-0005-3982-5303
dc.authorid0000-0001-7347-5339
dc.authorid0000-0002-9336-0552
dc.authorid0000-0002-2647-6416
dc.authorid0009-0007-0299-5549
dc.authorid0000-0003-1037-6477
dc.authorid0000-0003-0605-1741
dc.contributor.authorOzdemir, Ozkan
dc.contributor.authorBychkovsky, Brittany L.
dc.contributor.authorUnal, Busra
dc.contributor.authorOnder, Gizem
dc.contributor.authorAmanvermez, Ufuk
dc.contributor.authorAydin, Eylul
dc.contributor.authorAgaoglu, Nihat Bugra
dc.date.accessioned2026-04-04T18:56:06Z
dc.date.available2026-04-04T18:56:06Z
dc.date.issued2024
dc.departmentİstanbul Bilgi Üniversitesi
dc.description.abstractBackground and Objectives: Checkpoint kinase 2 (CHEK2) is a tumor suppressor gene involved in DNA repair and cell cycle regulation. Pathogenic or likely pathogenic (P/LP) variants in CHEK2 are associated with increased cancer risk. Conversely, recent large cohort studies have identified certain variants that, despite being classified as P/LP by in silico analysis, are considered low risk. Thus, the genotype-phenotype correlations of CHEK2 require a better understanding. In this study, we aimed to characterize germline CHEK2 variants from a group of individuals who applied to cancer genetic clinics in the Marmara Region of T & uuml;rkiye. We also aimed to assess the phenotypic impacts of these variants by using a new score of statistically significant in silico predictors (SSIPs). Methods: We analyzed 1707 individuals with high risk cancer predisposition, focusing on germline CHEK2 variants, using SSIP scores and population-specific data. Results: CHEK2 variants appeared in approximately 8% of cases. The SSIP scores indicated that the missense mutation, p.Arg117Gly, significantly impairs DNA repair. Almost half of the variants had higher allele frequencies than the variants listed in the Genome Aggregation Database (gnomAD), and three variants had significantly higher frequencies compared to the variants listed on the Turkish Variome database (p.Thr476Met, p.Arg137Gln, c.592+3A>T), emphasizing the importance of population-specific data. Conclusions: This comprehensive analysis of CHEK2 variants in the Turkish population provides crucial insights for cancer geneticists and oncologists. Our findings will help to enhance the evaluation and management of cancer predisposition associated with CHEK2 in T & uuml;rkiye and other regions that have significant Turkish populations.
dc.description.sponsorshipTUBITAK BIdot;DEB [1059B192100905]; TUBIdot;TAK-BIDEB 2244 Industrial Ph.D. Program [118C082]
dc.description.sponsorshipN.B.A. was supported by the scholarship number 1059B192100905 within the framework of the 2219-International Postdoctoral Research Scholarship Program provided by TUBITAK B & Idot;DEB. Ilayda Sahin is funded by TUB & Idot;TAK-BIDEB 2244 Industrial Ph.D. Program (grant number 118C082).
dc.identifier.doi10.3390/cancers16223876
dc.identifier.doi10.3390/cancers16223876
dc.identifier.issn2072-6694
dc.identifier.issue22
dc.identifier.pmid39594831
dc.identifier.scopus2-s2.0-85211025793
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/cancers16223876
dc.identifier.urihttps://hdl.handle.net/11411/10693
dc.identifier.volume16
dc.identifier.wosWOS:001364866200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofCancers
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260402
dc.snmzKA_Scopus_20260402
dc.subjectCheckpoint Kinase 2 (Chek2)
dc.subjectCancer Predisposition
dc.subjectVariant Interpretation
dc.subjectVariant Of Uncertain Significance (Vus)
dc.subjectStatistically Significant In Silico Predictor (Ssip)
dc.titleMolecular and In Silico Analysis of the CHEK2 Gene in Individuals with High Risk of Cancer Predisposition from Turkiye
dc.typeArticle

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