Promiscuous Mutations Activate the Noncanonical NF-kappaB Pathway in Multiple Myeloma

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2007 Aug 19

PMID 17692805

Citations 511

Authors

Jonathan J Keats

Rafael Fonseca

Marta Chesi

Roelandt Schop

Angela Baker

Wee-Joo Chng

Scott Van Wier

Rodger Tiedemann

Chang-Xin Shi

Michael Sebag

Esteban Braggio

Travis Henry

Yuan-Xiao Zhu

Homer Fogle

Tammy Price-Troska

Gregory Ahmann

Catherine Mancini

Leslie A Brents

Shaji Kumar

Philip Greipp

Angela Dispenzieri

Barb Bryant

George Mulligan

Laurakay Bruhn

Michael Barrett

Riccardo Valdez

Jeff Trent

A Keith Stewart

John Carpten

P Leif Bergsagel

Affiliations

Soon will be listed here.

Abstract

Activation of NF-kappaB 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-kappaB 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-kappaB pathway, with the single most common abnormality being inactivation of TRAF3. These results highlight the critical importance of the NF-kappaB pathway in the pathogenesis of multiple myeloma.

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