Haematologica, Vol 93, Issue 7, e53 doi:10.3324/haematol.13190
Copyright © 2008 by Ferrata Storti Foundation
Comment to: The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 2007; 92:1335-1342
P Bertrand,
C Maingonnat,
P Ruminy,
H Tilly,
C Bastard
INSERM U918, European Institute for Peptides Research (IFRMP23), Rouen, F-76038, France ; Centre Henri Becquerel, Department of Hematology, Rouen, F-76038, France
Correspondence: Dr. P Bertrand, laboratoire de Génétique Oncologique, Centre Henri Becquerel, rue d’Amiens, 76038 Rouen cedex, France. Phone: international +232.082.549. Fax: international +232.082.578. E-mail:pbertrand{at}rouen.fnclcc.fr
In a series of sixteen cases of diffuse large B-cell lymphomas (DLBCL) with t(14;18)(q32;q21) and 8q24/MYC rearrangements, le Gouill et al.1 report one case with a t(8;9)(q24;p13) translocation. They assert, what is not true, that this 8q24/MYC translocation variant was never reported in DLBCL before. In a recent article,2 we described a series of B-cell lymphomas carrying 8q24 rearrangements with non-immunoglobulin partners. Among them were three cases harbouring a t(8;9)(q24;p13) translocation, each of them found in DLBCLs with a t(14;18). In the discussion, le Gouill et al write that PAX5 was identified as the partner gene but do not provide any indication regarding their technical approach, nor any experimental result. We cannot agree with this way to deliver such an affirmation, as searching for PAX5 rearrangement in our cases, we found a more complex situation in all cases. In our work, two breakpoints from the t(8;9) were cloned and a third one mapped using FISH. All three breakpoints were located several hundred kilobases upstream from PAX5. In one cloned case the breakpoint was located upstream ZBTB5 exon2 and in the other case upstream ZCCHC7. Molecular cytogenetics of the third case showed that the breakpoint was inside ZCCHC7. RT PCR experiments showed that these two genes were expressed (not shown). To assess a possible distant effect of the translocation on PAX5 regulation, we measured its relative expression by real-time quantitative RT PCR using the Taqman technology. Primers and probe were: 5'-TCCCAGCTTCCAGTCACAGC-3', 5'-ATCCGTGCT-CACCGAGGAC-3', and 5'-CCACTGGCTCCGTGAC GCAGG-3', respectively. Eleven DLBCL with a t(14;18) but without 9p13 rearrangement were used as controls. Relative expression levels (mean[95% confidence interval]) for controls and t(8;9) translocations were 0.661 [0.397–0.925] and 0.709 [0.349–1.068], respectively.
The absence of a significant difference of PAX5 expression in samples with/without the t(8;9), together with distant breakpoints from the gene let us to conclude that PAX5 cannot be considered, in our series, as the partner gene of the translocation. Our three cases displayed breakpoints dispersed on a 200–300kb region and we do not exclude the possibility that, in other t(8,9), a breakpoint located more closely to PAX5 could deregulate its expression. However, this must be demonstrated and rather than affirmed.
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References
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- Le Gouill S, Talmant P, Touzeau C, Moreau A, Garand R, Juge-Morineau N, et al. The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 2007;92:1335-42.[Abstract/Free Full Text]
- Bertrand P, Bastard C, Maingonnat C, Jardin F, Maisonneuve C, Courel MN, et al. Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas. Leukemia 2007;21:515-23.[CrossRef][ISI][Medline]
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