دورية أكاديمية
Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
| العنوان: | Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma |
|---|---|
| المؤلفون: | Mellid, Sara, Coloma, Javier, Calsina, Bruna, Monteagudo, María, Roldán Romero, Juan M., Santos, María, Leandro García, Luis J., Lanillos, Javier, Martínez Montes, Ángel M., Rodríguez Antona, Cristina, Montero Conde, Cristina, Martínez López, J, Ayala, Rosa, Matias-Guiu, Xavier, Robledo, Mercedes, Cascón, Alberto |
| المصدر: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
| بيانات النشر: | MDPI |
| سنة النشر: | 2020 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Tumors, Càncer de tiroide, Thyroid gland cancer |
| الوصف: | Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 12 p.; application/pdf |
| اللغة: | English |
| العلاقة: | Reproducció del document publicat a: https://doi.org/10.3390/cancers12113304Test; Cancers, 2020, vol. 12, num.11; https://doi.org/10.3390/cancers12113304Test; http://hdl.handle.net/2445/173844Test |
| الإتاحة: | https://doi.org/10.3390/cancers12113304Test http://hdl.handle.net/2445/173844Test |
| حقوق: | cc by (c) Mellid et al., 2020 ; http://creativecommons.org/licenses/by/3.0/esTest/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.33D4F79C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |