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Genetic lesions of the TRAF 3 and MAP 3K14 genes in classical H odgkin lymphoma
Author(s) -
Otto Claudia,
Giefing Maciej,
Massow Anne,
Vater Inga,
Gesk Stefan,
Schlesner Matthias,
Richter Julia,
Klapper Wolfram,
Hansmann MartinLeo,
Siebert Reiner,
Küppers Ralf
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09113.x
Subject(s) - gene , lymphoma , biology , genetics , immunology
Summary Hodgkin and Reed/Sternberg (HRS) cells in classical H odgkin lymphoma ( cHL ) show constitutive activation of nuclear factor ( NF )‐κB. Several genetic lesions contribute to this deregulated NF ‐κB activity. Here, we analysed two further NF ‐κB regulators for genetic lesions, the inhibitory factor TRAF 3 and the key signalling component of the alternative NF ‐κB pathway, MAP 3K14 ( NIK ). Single nucleotide polymorphism ( SNP ) array analysis of c HL cell lines revealed a uniparental disomy of the long arm of chromosome 14 associated with a biallelic deletion of TRAF 3 located on this chromosome in cell line U‐HO1. Cloning of the deletion breakpoint showed a 123 371 bp deletion. No inactivating mutations of TRAF 3 were found in six other c HL cell lines or in microdissected HRS cells from seven cHL . However, in primary c HL samples interphase cytogenetic analyses revealed signal patterns indicating monoallelic deletion of TRAF 3 in 3/20 other cases. SNP array analysis revealed a gain of copy number for MAP 3K14 in three c HL cell lines. Gains of MAP 3K14 were detected in 5/16 cases of primary cHL . In conclusion, in rare instances, HRS cells harbour inactivating mutations of the TRAF 3 gene and recurrently show gains of MAP 3K14 , indicating that more components of NF ‐κB signalling show genetic lesions in HRS cells than previously known.