Author/Authors :
Keats، نويسنده , , Jonathan J. and Fonseca، نويسنده , , Rafael and Chesi، نويسنده , , Marta and Schop، نويسنده , , Roelandt and Baker، نويسنده , , Angela and Chng، نويسنده , , Wee-Joo and Van Wier، نويسنده , , Scott and Tiedemann، نويسنده , , Rodger and Shi، نويسنده , , Chang-Xin and Sebag، نويسنده , , Michael and Braggio، نويسنده , , Esteban and Henry، نويسنده , , Travis and Zhu، نويسنده , , Yuan-Xiao and Fogle، نويسنده , , Homer and Price-Troska، نويسنده , , Tammy and Ahmann، نويسنده , , Gregory and Mancini، نويسنده , , Catherine and Brents، نويسنده , , Leslie A. and Kumar، نويسنده , , Shaji and Greipp، نويسنده , , Philip and Dispenzieri، نويسنده , , Angela and Bryant، نويسنده , , Barb and Mulligan، نويسنده , , George and Bruhn، نويسنده , , Laurakay and Barrett، نويسنده , , Michael and Valdez، نويسنده , , Riccardo and Trent، نويسنده , , Jeff and Stewart، نويسنده , , A. Keith and Carpten، نويسنده , , John and Bergsagel، نويسنده , , P. Leif، نويسنده ,
Abstract :
Summary
tion 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.
