title: The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia.
abstract: To identify new cytogenetic abnormalities associated with leukemogenesis or disease outcome, T-cell acute lymphoblastic leukemia (T-ALL) patient samples were analyzed by means of the array-comparative genome hybridization technique (array-CGH). Here, we report the identification of a new recurrent and cryptic deletion on chromosome 11 (del(11)(p12p13)) in about 4% (6/138) of pediatric T-ALL patients. Detailed molecular-cytogenetic analysis revealed that this deletion activates the LMO2 oncogene in 4 of 6 del(11)(p12p13)-positive T-ALL patients, in the same manner as in patients with an LMO2 translocation (9/138). The LMO2 activation mechanism of this deletion is loss of a negative regulatory region upstream of LMO2, causing activation of the proximal LMO2 promoter. LMO2 rearrangements, including this del(11)(p12p13) and t(11;14) (p13;q11) or t(7;11)(q35;p13), were found in the absence of other recurrent cytogenetic abnormalities involving HOX11L2, HOX11, CALM-AF10, TAL1, MLL, or MYC. LMO2 abnormalities represent about 9% (13/138) of pediatric T-ALL cases and are more frequent in pediatric T-ALL than appreciated until now.
authors.affiliation: Erasmus MC/Sophia Children's Hospital, Department of Pediatric Oncology/Hematology, 3000 CB Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
authors.forename: Martine
authors.initials: M
authors.lastname: van Grotel
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Tryggvi
authors.initials: T
authors.lastname: Helgason
authors.forename: Jessica
authors.initials: J
authors.lastname: Buijs-Gladdines
authors.forename: Monique
authors.initials: M
authors.lastname: Passier
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: van Wering
authors.forename: Anjo J P
authors.initials: AJ
authors.lastname: Veerman
authors.forename: Willem A
authors.initials: WA
authors.lastname: Kamps
authors.forename: Jules P P
authors.initials: JP
authors.lastname: Meijerink
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002648:Child; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D014178:Translocation, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins