title: No evidence for the JAK2 (V617F) or JAK2 exon 12 mutations in primary mediastinal large B-cell lymphoma.
abstract: Dysregulated JAK2 signaling has been shown to play a significant role in the pathogenesis of myeloproliferative disorders. Recently, our work comparing gene expression signatures of primary mediastinal large B-cell lymphomas (PMLBCL) versus nodal diffuse large B-cell lymphomas revealed a relative increase in JAK2 transcripts in the former, suggesting a role for increased JAK2 signaling in a subset of these tumors. Given the likelihood of increased JAK2 signaling in PMLBCL, we sought to determine whether JAK2 activating mutations were an alternative mechanism for increased JAK2 signaling in untreated PMLBCLs. We performed amplification refractory mutation analysis for the JAK2 (V617F) mutation and bidirectional sequencing for the recently described JAK2 exon 12 mutations on genomic DNA isolated from a well-characterized cohort of PMLBCLs. No evidence of the mutant JAK2 (V617F) allele or JAK2 exon 12 mutations was detected in 31 PMLBCL cases tested. Analysis using cell lines derived from PMLBCLs (n = 1) and from the molecularly similar classic Hodgkin lymphoma (n = 4) also failed to reveal involvement of a mutant JAK2 allele. Taken together, these results suggest that JAK2 signaling in PMLBCLs occurs by mechanisms distinct from JAK2 (V617F) or JAK2 exon 12 activating mutations.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wu
authors.forename: Bethany
authors.initials: B
authors.lastname: Dutra
authors.forename: Neal
authors.initials: N
authors.lastname: Lindeman
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takeyama
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Harris
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: Janina
authors.initials: J
authors.lastname: Longtine
authors.forename: Margaret
authors.initials: M
authors.lastname: Shipp
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
mesh_terms: D005091:Exons; D005787:Gene Frequency; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000175:diagnosis* / Q000235:genetics*; D008479:Mediastinal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2
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