title: High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations.
abstract: To identify cooperating lesions in core-binding factor acute myeloid leukemia, we performed single-nucleotide polymorphism-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). Approximately one-half of the 7q deletions were detectable only by single-nucleotide polymorphism-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single noncoding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region of 1p (NRAS) and 4q (TET2). Analysis of relapse samples identified recurrent MDRs at 3q13.31 (12.2%), 5q (4.9%), and 17p (4.9%), with the 3q13.31 region containing only LSAMP, a putative tumor suppressor. Determining the role of these lesions in leukemogenesis and drug resistance should provide important insights into core-binding factor acute myeloid leukemia.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Germany.
authors.forename: Michael W M
authors.initials: MW
authors.lastname: Kühn
authors.forename: Ina
authors.initials: I
authors.lastname: Radtke
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Salil
authors.initials: S
authors.lastname: Goorha
authors.forename: Jinjun
authors.initials: J
authors.lastname: Cheng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Edelmann
authors.forename: Juliane
authors.initials: J
authors.lastname: Gohlke
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Asmaa
authors.initials: A
authors.lastname: Quessar
authors.forename: Raul
authors.initials: R
authors.lastname: Ribeiro
authors.forename: Verena I
authors.initials: VI
authors.lastname: Gaidzik
authors.forename: Sheila
authors.initials: S
authors.lastname: Shurtleff
authors.forename: Jan
authors.initials: J
authors.lastname: Krönke
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
mesh_terms: D000208:Acute Disease; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D050660:Core Binding Factors / Q000235:genetics*; D056915:DNA Copy Number Variations; D020869:Gene Expression Profiling / Q000379:methods*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence
chemical_list: D050660:Core Binding Factors; D015514:Oncogene Proteins, Fusion