Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma.

Abstract:

:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-a subtype of Hodgkin lymphoma (HL)-is characterized by a low content of tumor cells, the lymphocyte predominant (LP) cells. Transformation into diffuse large B-cell lymphoma (DLBCL) occurs in about 10% of patients. We performed whole-genome mutation analysis of the DLBCL components from two composite lymphomas consisting of clonally related NLPHL and DLBCL as a means to identify candidate tumor suppressor genes and oncogenes in NLPHL. The analysis of LP cells for selected mutations of the DLBCL revealed that most mutations are also present in the LP cells, indicating a close relationship between the two components. The analysis of 62 selected genes in NLPHL by targeted ultra-deep sequencing revealed three novel highly recurrently mutated genes (each mutated in ~50% of cases), that is, DUSP2, SGK1 and JUNB. SGK1 was expressed in the LP cells of primary NLPHL cases and in the NLPHL cell line DEV. Administration of an SGK1 inhibitor induced apoptosis in the NLPHL cell line DEV and the DLBCL cell line Farage, suggesting a pathogenetic role of SGK1 in the LP and DLBCL cells. In summary, the present study identifies SGK1, DUSP2 and JUNB as novel key players in the pathogenesis of NLPHL.

journal_name

Leukemia

journal_title

Leukemia

authors

Hartmann S,Schuhmacher B,Rausch T,Fuller L,Döring C,Weniger M,Lollies A,Weiser C,Thurner L,Rengstl B,Brunnberg U,Vornanen M,Pfreundschuh M,Benes V,Küppers R,Newrzela S,Hansmann ML

doi

10.1038/leu.2015.328

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

844-53

issue

4

eissn

0887-6924

issn

1476-5551

pii

leu2015328

journal_volume

30

pub_type

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