دورية أكاديمية
The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution
| العنوان: | The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution |
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| المؤلفون: | MOSQUERA ORGUEIRA, ADRIAN, Antelo Rodríguez, Beatriz, Alonso Vence, Natalia, Díaz Arias, José, Díaz Varela, Nicolás, Pérez Encinas, Manuel Mateo, Allegue Toscano, C., Goiricelaya Seco, E. M., Carracedo Álvarez, Ángel, Bello López, José Luis |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Phosphoprotein Phosphatases, GTP-Binding Protein alpha Subunits, Survival Analysis, MAP Kinase Kinase Kinase 4, Humans, Association, Leukemia, Germ-Line Mutation, Genetic Predisposition to Disease, Prognosis, Gene Regulatory Networks, MAP cinasa cinasa cinasa 4, pronóstico, subunidades alfa de las proteínas de unión al GTP, humanos, análisis de supervivencia, fosfoproteína fosfatasas, leucemia, asociación, predisposición genética a la enfermedad, mutación de la línea germinal, redes génicas reguladoras, CHUS |
| الوصف: | BACKGROUND: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth. METHODS: Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated. RESULTS: Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNalpha13 and Nitric oxide was associated with overall survival. CONCLUSION: Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1471-2407 |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542042/pdf/12885_2019_Article_5628.pdfTest; https://www.ncbi.nlm.nih.gov/pubmed/31142279Test; http://hdl.handle.net/20.500.11940/15774Test; 31789 |
| DOI: | 10.1186/s12885-019-5628-y |
| الإتاحة: | https://doi.org/20.500.11940/15774Test https://doi.org/10.1186/s12885-019-5628-yTest https://hdl.handle.net/20.500.11940/15774Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542042/pdf/12885_2019_Article_5628.pdfTest https://www.ncbi.nlm.nih.gov/pubmed/31142279Test |
| حقوق: | Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0Test/ ; openAccess |
| رقم الانضمام: | edsbas.ECB6BD1A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14712407 |
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| DOI: | 10.1186/s12885-019-5628-y |