Submicroscopic genomic imbalances in burkitt lymphomas/leukemias: Association with age and further evidence that 8q24/MYC translocations are not sufficient for leukemogenesis
2013 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 52, no 4, 370-377 p.Article in journal (Refereed) Published
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 121) than did the childhood cases (median 1.5; range 05) (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.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2013. Vol. 52, no 4, 370-377 p.
IdentifiersURN: urn:nbn:se:liu:diva-90183DOI: 10.1002/gcc.22034ISI: 000314981600003OAI: oai:DiVA.org:liu-90183DiVA: diva2:613156
Funding Agencies|Swedish Childhood Cancer Foundation||Swedish Cancer Society||Swedish Research Council||2013-03-262013-03-212013-04-05