The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias
Open accessAbstract
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.
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Metadata
- Authors
- for The St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project, Andersson, A. K., Ma, J., Wang, J., Chen, X., Gedman, A. L., 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., Becksfort, J., Gupta, P., Payne-Turner, D., Vadodaria, B., Boggs, K., Yergeau, D., Manne, J., Song, G., Edmonson, M., Nagahawatte, P., Wei, L., Cheng, C., Pei, D., Sutton, R., Venn, N. C., Chetcuti, A., Rush, A., Catchpoole, D., Heldrup, J., Fioretos, T., Lu, C., Ding, L., Pui, C.-H., Shurtleff, S., Mullighan, C. G., Mardis, E. R., Wilson, R. K., Gruber, T. A., Zhang, J., & Downing, J. R.
- Venue
- Nature Genetics
- Published
- 2015-03-02
- Volume
- 47
- Issue
- 4
- Pages
- 330-337
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2047965845
- Cited by
- 490
- References
- 67
- FWCI
- 45.94
- Type
- journal article
- Language
- en
- Open access
- green
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- for The St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project, Andersson, A. K., Ma, J., Wang, J., Chen, X., Gedman, A. L., 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., . . . Downing, J. R. (2015). The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nature Genetics. https://doi.org/10.1038/ng.3230
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