The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
Författare
Summary, in English
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.
Avdelning/ar
- MLL-rearrangerad leukemi hos spädbarn
- Avdelningen för klinisk genetik
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Pediatrik, Lund
Publiceringsår
2015
Språk
Engelska
Sidor
192-330
Publikation/Tidskrift/Serie
Nature Genetics
Volym
47
Issue
4
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Medical Genetics
Status
Published
Forskningsgrupp
- The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
ISBN/ISSN/Övrigt
- ISSN: 1546-1718