title: Submicroscopic genomic imbalances in Burkitt lymphomas/leukemias: association with age and further evidence that 8q24/MYC translocations are not sufficient for leukemogenesis.
abstract: Chromosome banding analyses reveal secondary chromosome abnormalities in addition to the MYC translocations t(8;14)(q24;q32), t(8;22)(q24;q11), and t(2;8)(p11;q24) in 60%-80% of Burkitt lymphomas/leukemias (BL). The high incidence of such aberrations indicates that additional changes are important, perhaps necessary, for malignant transformation, i.e., the 8q24/MYC rearrangements may not be sufficient. To investigate this possibility, we performed single nucleotide polymorphism (SNP) array analysis on 20 cases of 8q24/MYC-positive BL. Nineteen (95%) harbored genomic imbalances; the only case without such aberrations displayed secondary changes by chromosome banding analysis. Thus, all BL cases had abnormalities in addition to the 8q24 translocation. The adult cases harbored more changes (median 3; range 1-21) than did the childhood cases (median 1.5; range 0-5) (P = 0.034). Several recurrent aberrations were detected by SNP array analysis, in particular losses of 6q14.1-q22.33, 9p21.3, and 13q14.2-q14.3, gains of 1q23.3-q31.3, chromosome 7, 13q31.3, and partial uniparental isodisomies for 6p12.2-pter, 9p23-pter, and 17p11.2-pter. The molecular genetic consequences of these changes include deletions of the CDKN2A and TP53 genes, and gains/losses of several genes, such as MIR17HG and E2F2K, involved in the MYC pathway. Thus, deregulation of the MYC pathway, both directly through the 8q24/MYC translocation and indirectly through secondary genomic imbalances, may be essential not only for the initiation but also for the progression of BL.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. catarina.lundin@med.lu.se
authors.forename: Catarina
authors.initials: C
authors.lastname: Lundin
authors.forename: Lars
authors.initials: L
authors.lastname: Hjorth
authors.forename: Mikael
authors.initials: M
authors.lastname: Behrendtz
authors.forename: Mats
authors.initials: M
authors.lastname: Ehinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Biloglav
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D016271:Proto-Oncogene Proteins c-myc