The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms
| العنوان: | The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms |
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| المؤلفون: | Stanley Pounds, Lindsey E. Montefiori, Charles G. Mullighan, Jamie L. Maciaszek, Yanling Liu, Jing Ma, Jennifer Kamens, Tanja A. Gruber, Michael P. Walsh, Samuel W. Brady, Kim E. Nichols, Jinghui Zhang, Ryan Hiltenbrand, Jeffrey E. Rubnitz, Xiao-Long Chen, Scott Newman, Priyadarshini Kumar, J. Robert Michael, Huiyun Wu, John Easton, Cristyn Branstetter, Michael Walsh, Jeffery M. Klco, Xiaotu Ma, Jason R. Schwartz, Gang Wu, Tamara Westover, Guangchun Song |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Lineage (genetic), Myeloid, MECOM, Science, General Physics and Astronomy, Bioinformatics, Article, Acute myeloid leukaemia, General Biochemistry, Genetics and Molecular Biology, Germline, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, Cancer genomics, medicine, Humans, Child, Exome, Exome sequencing, Multidisciplinary, biology, business.industry, Neoplasms, Second Primary, Genomics, Histone-Lysine N-Methyltransferase, General Chemistry, Prognosis, medicine.disease, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute, Leukemia, 030104 developmental biology, medicine.anatomical_structure, KMT2A, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Mutation, biology.protein, Gene expression, business, Myelodysplastic syndrome, Myeloid-Lymphoid Leukemia Protein |
| الوصف: | Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 84 pediatric tMN cases (tMDS: n = 28, tAML: n = 56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases are unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms. Paediatric therapy-related myeloid neoplasms (tMN) have a dismal prognosis and have not been comprehensively profiled. Here the authors characterise the molecular landscape of 84 paediatric tMN patients, and find that, unlike adult tMNs, these do not emerge from pre-existing clones and that MECOM dysregulation is frequent. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d44690cd2877fa620c001b9907ba33bbTest https://doaj.org/article/fe707965968044aaa183257f76774e4dTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d44690cd2877fa620c001b9907ba33bb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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