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dc.contributor.authorHatipoğlu, Tevfik
dc.contributor.authorEsmeray Sönmez, Esra
dc.contributor.authorHu, Xiaozhou
dc.contributor.authorYuan, Hongling
dc.contributor.authorÖnal-Süzek, Tuğba
dc.date.accessioned2022-07-18T07:23:22Z
dc.date.available2022-07-18T07:23:22Z
dc.date.issued2022en_US
dc.identifier.citationHatipoğlu T, Esmeray Sönmez E, Hu X,Yuan H, Danyeli AE, Seyhanlı A,Önal-Süzek T, Zhang W, Akman B,Olgun A, Özkal S, Alacacıoğlu I˙,Özcan MA, You H and Küçük C (2022) Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non- Invasive Diagnosis and Prognosis. Front. Oncol. 12:870487. doi: 10.3389/fonc.2022.870487en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12809/10090
dc.description.abstractFollicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.en_US
dc.item-language.isoengen_US
dc.publisherFrontiers Media SAen_US
dc.relation.isversionof10.3389/fonc.2022.870487en_US
dc.item-rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectFollicular lymphomaen_US
dc.subjectLiquid biopsyen_US
dc.subjectcfDNA genotypingen_US
dc.titlePlasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosisen_US
dc.item-typearticleen_US
dc.contributor.departmentMÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümüen_US
dc.contributor.authorID0000-0002-3243-1759en_US
dc.contributor.institutionauthorÖnal-Süzek, Tuğba
dc.identifier.volume12en_US
dc.relation.journalFrontiers in Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - İdari Personel ve Öğrencien_US


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