<scp>RNAseq</scp> identification of <scp>FISH</scp>‐cryptic <scp>BCL6</scp>::<scp>TP63</scp> rearrangement in <scp>ALK</scp>‐negative anaplastic large‐cell lymphoma

Ahmed, Nada; Ketterling, Rhett P.; Nowakowski, Grzegorz S.; Dasari, Surendra; Feldman, Andrew L.

doi:10.1111/his.14674

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…On the other hand, cryptic TP63 rearrangements cannot formally be excluded, as recently described. 28 These latter would however not have been detected in previously published series based on FISH assays.…”

Section: Discussionmentioning

confidence: 73%

ALK-negative anaplastic large cell lymphoma with DUSP22 rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study

et al. 2022

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ALK-negative anaplastic large cell lymphoma (ALCL) comprises subgroups harboring rearrangements of DUSP22 (DUSP22-R) or TP63 (TP63-R). Two studies respectively reported 90% and 40% 5-year overall survival (OS) in 21 and 12 DUSP22-R/TP63-not rearranged (NR) patients, making the prognostic impact of DUSP22-R unclear. Here, 104 newly diagnosed ALK-negative ALCL patients (including 37 from first-line clinical trials) from the LYSA TENOMIC database were analyzed by break-apart FISH assays for DUSP22-R and TP63-R. There were 47/104 (45%) DUSP22-R and 2/93 (2%) TP63-R cases, including one DUSP22-R/TP63-R. DUSP22-R tumors showed more frequent CD3 expression (62% versus 35%, P=0.01), and less commonly a cytotoxic phenotype (27% versus 82%; P

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Section: Discussionmentioning

confidence: 73%

ALK-negative anaplastic large cell lymphoma with DUSP22 rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study

et al. 2022

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“…In other cases, such as the use of p63 IHC in identifying TP63- R, IHC facilitates a diagnostic approach to genetic subtyping but FISH is still required in a subset of cases 21. Importantly, false-negative FISH results due to cryptic structural alterations also can occur, as in the case of cryptic MYC- R in B-cell lymphomas34,35; we also recently identified a FISH-cryptic TP63- R in a case of ALK-negative ALCL 36. In the case of DUSP22- R, indeterminate FISH results occasionally occur in which the break-apart probe identifies loss of the 5′- DUSP22 signal and cannot distinguish between telomeric 6p deletion and an unbalanced DUSP22- R 37.…”

Section: Discussionmentioning

confidence: 90%

“…21 Importantly, false-negative FISH results due to cryptic structural alterations also can occur, as in the case of cryptic MYC-R in B-cell lymphomas 34,35 ; we also recently identified a FISH-cryptic TP63-R in a case of ALK-negative ALCL. 36 In the case of DUSP22-R, indeterminate FISH results occasionally occur in which the break-apart probe identifies loss of the 5′-DUSP22 signal and cannot distinguish between telomeric 6p deletion and an unbalanced DUSP22-R. 37 In the future, platforms other than FISH might be employed in genetic subtyping. A gene expression signature successfully identified high-grade B-cell lymphomas with FISH-cryptic MYC-R or BCL2-R 35 and we previously developed and validated a gene expression signature for DUSP22-R in ALCL.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Approach to Genetic Subtyping of Anaplastic Large Cell Lymphoma

Feldman¹,

Oishi

Ketterling³

et al. 2022

American Journal of Surgical Pathology

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Anaplastic large cell lymphoma (ALCL) can be classified genetically based on rearrangements (R) of the ALK, TP63, and/or DUSP22 genes. ALK-R defines a specific entity, ALK-positive ALCL, while DUSP22-R and TP63-R define subgroups of ALK-negative ALCLs with distinct clinicopathologic features. ALK-R and TP63-R produce oncogenic fusion proteins that can be detected by immunohistochemistry. ALK immunohistochemistry is an excellent surrogate for ALK-R and screening with p63 immunohistochemistry excludes TP63-R in two third of ALCLs. In contrast, DUSP22-R does not produce a fusion protein and its identification requires fluorescence in situ hybridization. However, DUSP22-R ALCL has a characteristic phenotype including negativity for cytotoxic markers and phospho-STAT3 Y705 . Recently, we also identified overexpression of the LEF1 transcription factor in DUSP22-R ALCL. Here, we sought to validate this finding and examine models for predicting DUSP22-R using immunohistochemistry for LEF1 and TIA1 or phospho-STAT3 Y705 . We evaluated these 3 markers in our original discovery cohort (n = 45) and in an independent validation cohort (n = 46) of ALCLs. The correlation between DUSP22-R and LEF1 expression replicated strongly in the validation cohort (P < 0.0001). In addition, we identified and validated a strategy using LEF1 and TIA1 immunohistochemistry that predicted DUSP22-R with positive and negative predictive values of 100% after exclusion of indeterminate cases and would eliminate the need for fluorescence in situ hybridization in 65% of ALK-negative ALCLs. This approach had similar results in identifying DUSP22-R in the related condition, lymphomatoid papulosis. Together with previous data, these findings support a 4-marker immunohistochemistry algorithm using ALK, LEF1, TIA1, and p63 for genetic subtyping of ALCL.

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Anaplastic large cell lymphomas with equivocal DUSP22 FISH results: recommendations for clinical reporting and diagnostic evaluation

Fadl,

Oishi,

Shi

et al. 2023

Human Pathology

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RNAseq identification of FISH‐cryptic BCL6::TP63 rearrangement in ALK‐negative anaplastic large‐cell lymphoma

Cited by 4 publications

References 6 publications

ALK-negative anaplastic large cell lymphoma with <i>DUSP22</i> rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study

ALK-negative anaplastic large cell lymphoma with <i>DUSP22</i> rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study

Immunohistochemical Approach to Genetic Subtyping of Anaplastic Large Cell Lymphoma

Anaplastic large cell lymphomas with equivocal DUSP22 FISH results: recommendations for clinical reporting and diagnostic evaluation

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