title: Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma.
abstract: Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin 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 TRAF3 and the key signalling component of the alternative NF-κB pathway, MAP3K14 (NIK). Single nucleotide polymorphism (SNP) array analysis of cHL cell lines revealed a uniparental disomy of the long arm of chromosome 14 associated with a biallelic deletion of TRAF3 located on this chromosome in cell line U-HO1. Cloning of the deletion breakpoint showed a 123 371 bp deletion. No inactivating mutations of TRAF3 were found in six other cHL cell lines or in microdissected HRS cells from seven cHL. However, in primary cHL samples interphase cytogenetic analyses revealed signal patterns indicating monoallelic deletion of TRAF3 in 3/20 other cases. SNP array analysis revealed a gain of copy number for MAP3K14 in three cHL cell lines. Gains of MAP3K14 were detected in 5/16 cases of primary cHL. In conclusion, in rare instances, HRS cells harbour inactivating mutations of the TRAF3 gene and recurrently show gains of MAP3K14, indicating that more components of NF-κB signalling show genetic lesions in HRS cells than previously known.
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Otto
authors.forename: Maciej
authors.initials: M
authors.lastname: Giefing
authors.forename: Anne
authors.initials: A
authors.lastname: Massow
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Matthias
authors.initials: M
authors.lastname: Schlesner
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002648:Child; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D048008:TNF Receptor-Associated Factor 3; D015534:Trans-Activators; D000097782:NF-kappaB-Inducing Kinase; D000099232:Proto-Oncogene Protein Spi-1; C090656:TRAF3 protein, human