Partial trisomy 11, dup(11)(q23q13), as a defect characterizing lymphomas with Burkitt pathomorphology without MYC gene rearrangement

Abstract

Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma characterized by specific morphological and immunophenotypic features. The basic genetic feature of BL is the rearrangement of MYC gene, visible as t(8;14)(q24;q32) translocation or its variant. However, some lymphomas with characteristic BL morphology are nowadays diagnosed as B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL (Inter-DLBCL/BL) for biological or clinical reasons. We present four lymphomas without the MYC rearrangement presented typical Burkitt morphology, FCM immunophenotype with some deviations when compared to a typical BL. The cases were finally diagnosed as Inter-DLBCL/BL. All of them presented a recurrent abnormality within the chromosome 11: dup(11)(q23q13). We suppose that the dup(11)(q23q13), in absence of the MYC gene rearrangement, is connected with borderline lymphomas with a morphology similar or identical to that of the Burkitt lymphoma. Identifying such an aberration may be helpful in the diagnostics of Inter-DLBCL/BL eventually forming a distinct subgroup of lymphomas.

A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma

“…This result led them to reclassify the cases as intermediate between DLBCL and BL because of the immunophenotypical and genetic features. 8 Similarly, Poirel et al observed by cytogenetic review of childhood mature B-cell non-Hodgkin lymphomas that the 13 cases classified as BL without a detectable MYC translocation shared alterations with the MYC-positive BL except for the existence of more frequent aneuploidy and the presence of a derivative chromosome 11q. 11 In the present study, we investigated the incidence of MYC-negative BL defined by gene expression analysis using 2 different classifiers.…”

“…5,[7][8][9] Nevertheless, caution is warranted before concluding that these indeed represent true MYC-negative BL, because the scattering of breakpoints in the MYC and IG loci along with small insertions of one locus into the other can render MYC breaks undetectable even if an extensive set of FISH probes is applied. 10 Moreover, there is no gold standard to define BL in the absence of an MYC break.…”

“…Twelve MYC-negative lymphomas, 5 of which were previously reported, 8,13,14 and SU-DHL-5 and HT cell lines, derived from MYC-negative high-grade B-cell lymphomas (www.dsmz.de), were included for cytogenetic and genetic analyses. Information on case selection is detailed in the supplemental Methods and in supplemental Table 1, available on the Blood Web site.…”

“…Methods on cases 4 through 7 have been previously published. 8 Copy number and mutational analyses SNP 6.0 array (Affymetrix, Santa Clara, CA) was used in cases 1 through 3 and 8 and cell lines as previously described. 18 Cases 4 through 7 and 9 through 12 were analyzed using Agilent Human CGH Microarray platforms owing to methodologic requirements for formalin fixed paraffin embedded tissues (GEO-Number GSE47508).…”

“…Because a recent cytogenetic study suggested a similar pattern appearing as partial trisomy 11 resulting from a dup(11)(q23q13) to characterize lymphomas with BL morphology without MYC gene rearrangement, 8 an extensive genetic investigation of this chromosome 11 aberration pattern was initiated. In addition to the cases described by Pienkowska-Grela et al, 8 we identified 8 lymphomas with features of BL predominantly in children and young adults. The mean age of the whole series was 20.5 years (range 6-76).…”