TY - JOUR
T1 - JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyterich large B-cell lymphoma
AU - Schuhmacher, Bianca
AU - Bein, Julia
AU - Rausch, Tobias
AU - Benes, Vladimir
AU - Tousseyn, Thomas
AU - Vornanen, Martine
AU - Ponzoni, Maurilio
AU - Thurner, Lorenz
AU - Gascoyne, Randy
AU - Steidl, Christian
AU - Küppers, Ralf
AU - Hansmann, Martin Leo
AU - Hartmann, Sylvia
PY - 2019/1/31
Y1 - 2019/1/31
N2 - T-cell/histiocyte-rich large B-cell lymphoma is a rare aggressive lymphoma showing histopathological overlap with nodular lymphocyte- predominant Hodgkin lymphoma. Despite differences in tumor microenvironment and clinical behavior, the tumor cells of both entities show remarkable similarities, suggesting that both lymphomas might represent a spectrum of the same disease. To address this issue, we investigated whether these entities share mutations. Ultra-deep targeted resequencing of six typical and 11 histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma, and nine cases of T-cell/histiocyte-rich large B-cell lymphoma revealed that genes recurrently mutated in nodular lymphocyte-predominant Hodgkin lymphoma are affected by mutations at similar frequencies in T-cell/histiocyte- rich large B-cell lymphoma. The most recurrently mutated genes were JUNB, DUSP2, SGK1, SOCS1 and CREBBP, which harbored mutations more frequently in T-cell/histiocyte-rich large B-cell lymphoma and the histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma than in its typical form. Mutations in JUNB, DUSP2, SGK1 and SOCS1 were highly enriched for somatic hypermutation hotspot sites, suggesting an important role of aberrant somatic hypermutation in the generation of these somatic mutations and thus in the pathogenesis of both lymphoma entities. Mutations in JUNB are generally rarely observed in malignant lymphomas and thus are relatively specific for nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma at such high frequencies (5/17 and 5/9 cases with JUNB mutations, respectively). Taken together, the findings of the present study further support a close relationship between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte- predominant Hodgkin lymphoma by showing that they share highly recurrent genetic lesions.
AB - T-cell/histiocyte-rich large B-cell lymphoma is a rare aggressive lymphoma showing histopathological overlap with nodular lymphocyte- predominant Hodgkin lymphoma. Despite differences in tumor microenvironment and clinical behavior, the tumor cells of both entities show remarkable similarities, suggesting that both lymphomas might represent a spectrum of the same disease. To address this issue, we investigated whether these entities share mutations. Ultra-deep targeted resequencing of six typical and 11 histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma, and nine cases of T-cell/histiocyte-rich large B-cell lymphoma revealed that genes recurrently mutated in nodular lymphocyte-predominant Hodgkin lymphoma are affected by mutations at similar frequencies in T-cell/histiocyte- rich large B-cell lymphoma. The most recurrently mutated genes were JUNB, DUSP2, SGK1, SOCS1 and CREBBP, which harbored mutations more frequently in T-cell/histiocyte-rich large B-cell lymphoma and the histopathological variants of nodular lymphocyte-predominant Hodgkin lymphoma than in its typical form. Mutations in JUNB, DUSP2, SGK1 and SOCS1 were highly enriched for somatic hypermutation hotspot sites, suggesting an important role of aberrant somatic hypermutation in the generation of these somatic mutations and thus in the pathogenesis of both lymphoma entities. Mutations in JUNB are generally rarely observed in malignant lymphomas and thus are relatively specific for nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma at such high frequencies (5/17 and 5/9 cases with JUNB mutations, respectively). Taken together, the findings of the present study further support a close relationship between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte- predominant Hodgkin lymphoma by showing that they share highly recurrent genetic lesions.
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U2 - 10.3324/haematol.2018.203224
DO - 10.3324/haematol.2018.203224
M3 - Article
C2 - 30213827
AN - SCOPUS:85059407068
VL - 104
SP - 330
EP - 337
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 2
ER -