[PDF][PDF] Promiscuous mutations activate the noncanonical NF-κB pathway in multiple myeloma

JJ Keats, R Fonseca, M Chesi, R Schop, A Baker… - Cancer cell, 2007 - cell.com
JJ Keats, R Fonseca, M Chesi, R Schop, A Baker, WJ Chng, S Van Wier, R Tiedemann
Cancer cell, 2007cell.com
Activation of NF-κB has been noted in many tumor types, however only rarely has this been
linked to an underlying genetic mutation. An integrated analysis of high-density
oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma
samples identified a promiscuous array of abnormalities contributing to the dysregulation of
NF-κB in approximately 20% of patients. We report mutations in ten genes causing the
inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2 and activation of NFKB1, NFKB2, CD40 …
Summary
Activation of NF-κB has been noted in many tumor types, however only rarely has this been linked to an underlying genetic mutation. An integrated analysis of high-density oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma samples identified a promiscuous array of abnormalities contributing to the dysregulation of NF-κB in approximately 20% of patients. We report mutations in ten genes causing the inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2 and activation of NFKB1, NFKB2, CD40, LTBR, TACI, and NIK that result primarily in constitutive activation of the noncanonical NF-κB pathway, with the single most common abnormality being inactivation of TRAF3. These results highlight the critical importance of the NF-κB pathway in the pathogenesis of multiple myeloma.
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