The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04

AUTHORS

Anna K Andersson, Jing Ma, Jianmin Wang, Xiang Chen, Amanda Larson Gedman, Jinjun Dang, Joy Nakitandwe, Linda Holmfeldt, Matthew Parker, John Easton, Robert Huether, Richard Kriwacki, Michael Rusch, Gang Wu, Yongjin Li, Heather Mulder, Susana Raimondi, Stanley Pounds, Guolian Kang, Lei Shi, Jared Becksfort, Pankaj Gupta, Debbie Payne-Turner, Bhavin Vadodaria, Kristy Boggs, Donald Yergeau, Jayanthi Manne, Guangchun Song, Michael Edmonson, Panduka Nagahawatte, Lei Wei, Cheng Cheng, Deqing Pei, Rosemary Sutton, Nicola C Venn, Albert Chetcuti, Amanda Rush, Daniel Catchpoole, Jesper Heldrup, Thoas Fioretos, Charles Lu, Li Ding, Ching-Hon Pui, Sheila Shurtleff, Charles G Mullighan, Elaine R Mardis, Richard K Wilson, Tanja A Gruber, Jinghui Zhang, James R Downing, 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. More... »

PAGES

330-337

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3230

    DOI

    http://dx.doi.org/10.1038/ng.3230

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1048699191

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25730765


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