Discovery of recurrent t (6; 7)(p25. 3; q32. 3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing

AL Feldman, A Dogan, DI Smith… - Blood, The Journal …, 2011 - ashpublications.org
AL Feldman, A Dogan, DI Smith, ME Law, SM Ansell, SH Johnson, JC Porcher, N Özsan…
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
The genetics of peripheral T-cell lymphomas are poorly understood. The most well-
characterized abnormalities are translocations involving ALK, occurring in approximately
half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs
lacking ALK translocations, we combined mate-pair DNA library construction, massively
parallel (“Next Generation”) sequencing, and a novel bioinformatic algorithm. We identified a
balanced translocation disrupting the DUSP22 phosphatase gene on 6p25. 3 and adjoining …
Abstract
The genetics of peripheral T-cell lymphomas are poorly understood. The most well-characterized abnormalities are translocations involving ALK, occurring in approximately half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs lacking ALK translocations, we combined mate-pair DNA library construction, massively parallel (“Next Generation”) sequencing, and a novel bioinformatic algorithm. We identified a balanced translocation disrupting the DUSP22 phosphatase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL. Using fluorescence in situ hybridization, we demonstrated that the t(6;7)(p25.3;q32.3) was recurrent in ALK-negative ALCLs. Furthermore, t(6;7)(p25.3;q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers.
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