دورية أكاديمية
Impact of somatic and germline mutations on the outcome of systemic mastocytosis
| العنوان: | Impact of somatic and germline mutations on the outcome of systemic mastocytosis |
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| المؤلفون: | Muñoz González, Javier Ignacio, Jara Acevedo, María, Alvarez-Twose, Iván, Merker, Jason D., Teodosio, Cristina, Hou, Yanli, Henriques, Ana, Roskin, Krishna M., Sanchez-Muñoz, Laura, Tsai, Albert G., Pontes-Geraz Caldas, Carolina, Matito, Almudena, Sánchez-Gallego, J. Ignacio, Mayado, Andrea, Dasilva Freire, Noelia, Gotlib, Jason R., Escribano, Luis, Orfao de Matos Correia e Vale, José Alberto, García Montero, Andrés Celestino |
| بيانات النشر: | Blood Advances |
| سنة النشر: | 2018 |
| المجموعة: | Universidad de Salamanca: Gredos (Gestión del Repositorio Documental de la Universidad de Salamanca) |
| مصطلحات موضوعية: | Systemic mastocytosis (SM), Genetic variants, Patients, KIT D816V, DNA, Narrow cells, Mastocytosis, Systemic, Cells, Genetic Variation, 3205.04 Hematología, variación genética, ADN, células, mastocitosis sistémica |
| الوصف: | [EN]Systemic mastocytosis (SM) is a highly heterogeneous disease with indolent and aggressive forms, with the mechanisms leading to malignant transformation still remaining to be elucidated. Here, we investigated the presence and frequency of genetic variants in 34 SM patients with multilineal KIT D816V mutations. Initial screening was performed by targeted sequencing of 410 genes in DNA extracted from purified bone marrow cells and hair from 12 patients with nonadvanced SM and 8 patients with advanced SM, followed by whole-genome sequencing (WGS) in 4 cases. Somatic mutations were further investigated in another 14 patients with advanced SM. Despite the fact that no common mutation other than KIT D816V was found in WGS analyses, targeted next-generation sequencing identified 67 nonsynonymous genetic variants involving 39 genes. Half of the mutations were somatic (mostly multilineal), whereas the other half were germline variants. The presence of ≥1 multilineal somatic mutation involving genes other than KIT D816V, ≥3 germline variants, and ≥1 multilineal mutation in the SRSF2, ASXL1, RUNX1, and/or EZH2 genes (S/A/R/E genes), in addition to skin lesions, splenomegaly, thrombocytopenia, low hemoglobin levels, and increased alkaline phosphatase and β2-microglobulin serum levels, were associated with a poorer patient outcome. However, the presence of ≥1 multilineal mutation, particularly involving S/A/R/E genes, was the only independent predictor for progression-free survival and overall survival in our cohort. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2473-9529 2473-9537 |
| العلاقة: | https://doi.org/10.1182/bloodadvances.2018020628Test; Munóz-González, J. I., Jara-Acevedo, M., Alvarez-Twose, I., Merker, J. D., Teodosio, C., Hou, Y., Henriques, A., Roskin, K. M., Sánchez-Muñoz, L., Tsai, A. G., Caldas, C., Matito, A., Sánchez-Gallego, J. I., Mayado, A., Dasilva-Freire, N., Gotlib, J. R., Escribano, L., Orfao, A., & García-Montero, A. C. (2018). Impact of somatic and germline mutations on the outcome of systemic mastocytosis. Blood Advances, 2(21), 2814–2828. https://doi.org/10.1182/bloodadvances.2018020628Test; http://hdl.handle.net/10366/146576Test |
| DOI: | 10.1182/bloodadvances.2018020628 |
| الإتاحة: | https://doi.org/10.1182/bloodadvances.2018020628Test http://hdl.handle.net/10366/146576Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3221E7F6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24739529 24739537 |
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| DOI: | 10.1182/bloodadvances.2018020628 |