title: The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q).
abstract: -7/del(7q) occurs in half of myeloid malignancies with adverse-risk cytogenetic features and is associated with poor survival. We identified the spectrum of mutations that co-occur with -7/del(7q) in 40 patients with de novo or therapy-related myeloid neoplasms. -7/del(7q) leukaemias have a distinct mutational profile characterized by low frequencies of alterations in genes encoding transcription factors, cohesin and DNA-methylation-related proteins. In contrast, RAS pathway activating mutations occurred in 50% of cases, a significantly higher frequency than other acute myeloid leukaemias and higher than previously reported. Our data provide guidance for which pathways may be most relevant in the treatment of adverse-risk myeloid leukaemia.
authors.affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA; Comprehensive Cancer Center, University of Chicago, Chicago, IL, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: McNerney
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Brown
authors.forename: April L
authors.initials: AL
authors.lastname: Peterson
authors.forename: Mekhala
authors.initials: M
authors.lastname: Banerjee
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: John
authors.initials: J
authors.lastname: Anastasi
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
mesh_terms: D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors
chemical_list: C080632:CUX1 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors
keywords: CUX1; monosomy 7; myeloid leukaemia