title: Molecular genetics of AML.
abstract: In the past decade, a series of technological advances have revolutionized our ability to interrogate cancer genomes, culminating in whole-genome sequencing, which provides genome-wide coverage at a single base-pair resolution. To date, the tumor genome has been sequenced in nearly 40 cases of acute myeloid leukemia (AML). On average, each AML genome contains approximately 400 mutations, including 6-26 coding mutations. The majority of these mutations are 'background' mutations that were acquired during normal aging of hematopoietic stem cells. Though comprehensively identifying 'driver' mutations remains a challenge, a number of novel driver mutations in AML have been identified through whole-genome sequencing. The digital nature of next-generation sequencing has revealed clonal heterogeneity in the majority of AML at diagnosis. Importantly, in some cases, a minor subclone contributed to relapse, suggesting the strategies to assess clonal heterogeneity are needed to optimize therapy. As sequencing technologies improve and costs decrease, it is likely that whole-genome sequencing of cancer cells will become commonplace in the diagnostic work-up of patients with AML and other cancers.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8007, Saint Louis, MO 63110, USA. dlink@dom.wustl.edu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
mesh_terms: D016922:Cellular Senescence / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation