The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

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title = "The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.",
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.",
author = "Anna Andersson and Jing Ma and Jianmin Wang and Xiang Chen and Gedman, {Amanda Larson} and Jinjun Dang and Joy Nakitandwe and Linda Holmfeldt and Matthew Parker and John Easton and Robert Huether and Richard Kriwacki and Michael Rusch and Gang Wu and Yongjin Li and Heather Mulder and Susana Raimondi and Stanley Pounds and Guolian Kang and Lei Shi and Jared Becksfort and Pankaj Gupta and Debbie Payne-Turner and Bhavin Vadodaria and Kristy Boggs and Donald Yergeau and Jayanthi Manne and Guangchun Song and Michael Edmonson and Panduka Nagahawatte and Lei Wei and Cheng Cheng and Deqing Pei and Rosemary Sutton and Venn, {Nicola C} and Albert Chetcuti and Amanda Rush and Daniel Catchpoole and Jesper Heldrup and Thoas Fioretos and Charles Lu and Li Ding and Ching-Hon Pui and Sheila Shurtleff and Mullighan, {Charles G} and Mardis, {Elaine R} and Wilson, {Richard K} and Gruber, {Tanja A} and Jinghui Zhang and Downing, {James R}",
year = "2015",
doi = "10.1038/ng.3230",
language = "English",
volume = "47",
pages = "330--U192",
journal = "Nature Genetics",
issn = "1546-1718",
publisher = "Nature Publishing Group",
number = "4",