Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas

Leukemia (2007) 21, 515523 & 2007 Nature Publishing Group All rights reserved 0887-6924/07 $30.00

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ORIGINAL ARTICLE Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas

P Bertrand, C Bastard, C Maingonnat, F Jardin, C Maisonneuve, M-N Courel, P Ruminy, J-M Picquenot, H Tilly Groupe dEtude des Prolifrations Lymphodes, Centre Henri Becquerel, INSERM U614, IFRMP23, Rouen, France

Chromosomal translocations joining the immunoglobulin (IG) and MYC genes have been extensively reported in Burkitts and non-Burkitts lymphomas but data concerning MYC rearrangements with non-IG partners are scarce. In this study, 8q24 breakpoints from 17 B-cell lymphomas involving non-IG loci were mapped by uorescence in situ hybridization (FISH). In seven cases the breakpoint was inside a small region encompassing MYC: in one t(7;8)(p12;q24) and two t(3;8)(q27;q24), it was telomeric to MYC whereas in four cases, one t(2;8)(p15;q24) and three t(8;9)(q24;p13) it was located in a 85 kb region encompassing MYC. In these seven cases, partner regions identied by FISH contained genes known to be involved in lymphomagenesis, namely BCL6, BCL11A, PAX5 and IKAROS. Breakpoints were cloned in two t(8;9)(q24;p13),2.5 and 7 kb downstream from MYC and several hundred kb 50 to PAX5 on chromosome 9, joining MYC to ZCCHC7 and to ZBTB5 exon 2, two genes encoding zinc-nger proteins. In these seven cases, MYC expression measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) was signicantly higher when compared to that of patients without 8q24 rearrangement (P 0.006). These results suggest that these rearrangements are the consequence of a non-random process targeting MYC together with non-IG genes involved in lymphocyte differentiation and lymphoma progression. Leukemia (2007) 21, 515523. doi:10.1038/sj.leu.2404529; published online 18 January 2007Keywords: MYC; lymphoma; breakpoint; FISH; gene expression

IntroductionThe t(8;14)(q24;q32) translocation is the major primary rearrangement observed in Burkitts lymphoma. Variant translocations, t(2;8)(p12;q24) and t(8;22)(q24;q11), are found in the remaining cases.1 These translocations lead to a deregulated MYC expression as a consequence of the vicinity of transcriptional enhancers of the IG genes. The MYC gene product is a transcription factor, whose overexpression plays a key role in the pathogenesis of the disease.2 Rearrangements of the 8q24 region with IG loci were also reported in other subtypes of nonHodgkins lymphomas (NHL) and are postulated to be secondary events which could be associated with disease...