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https://hdl.handle.net/2440/106072
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Type: | Journal article |
Title: | The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias |
Author: | Andersson, A. Ma, J. Wang, J. Chen, X. Gedman, A. Dang, J. Nakitandwe, J. Holmfeldt, L. Parker, M. Easton, J. Huether, R. Kriwacki, R. Rusch, M. Wu, G. Li, Y. Mulder, H. Raimondi, S. Pounds, S. Kang, G. Shi, L. et al. |
Citation: | Nature Genetics, 2015; 47(4):330-337 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Anna K Andersson ... Charles G Mullighan ... et al. for The St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project |
Abstract: | Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL. |
Keywords: | Acute lymphocytic leukaemia |
Description: | Includes 3 unnumbered pages at the end of the article. Published online 2 March 2015 |
Rights: | © 2015 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/ng.3230 |
Published version: | http://dx.doi.org/10.1038/ng.3230 |
Appears in Collections: | Aurora harvest 3 Pathology publications |
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