DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

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Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485.

PubMed ID
18987736 [ View in PubMed
]
Abstract

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Receptor-type tyrosine-protein kinase FLT3P36888Details
Multidrug resistance-associated protein 1P33527Details
Urokinase-type plasminogen activatorP00749Details
Serum paraoxonase/arylesterase 1P27169Details
Dihydropyrimidine dehydrogenase [NADP(+)]Q12882Details
Cystic fibrosis transmembrane conductance regulatorP13569Details
AromataseP11511Details
Methylenetetrahydrofolate reductaseP42898Details
Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrialO14521Details
Melanocyte-stimulating hormone receptorQ01726Details
Leptin receptorP48357Details
Induced myeloid leukemia cell differentiation protein Mcl-1Q07820Details
Multidrug resistance-associated protein 6O95255Details
TGF-beta receptor type-1P36897Details
Hepatocyte growth factor-regulated tyrosine kinase substrateO14964Details
Interleukin-1 receptor antagonist proteinP18510Details