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Prevalence and timing of TP53 mutations in del(17p) myeloma and effect on survival

Melody Chin,J. Sive,C. Allen,C. Roddie,S. Chavda,Dean Smith,P. Blombery,Kate Jones,G. Ryland,R. Popat,A. Rismani,Shirley D’Sa,N. Rabin,R. Gale,Kwee L Yong

Published 2017 in Blood Cancer Journal

ABSTRACT

The recent remarkable advances in multiple myeloma (MM) therapy and outcomes have had mixed impact on patients with adverse risk genetics, many of whom continue to have inferior outcomes. This applies particularly to deletion of chromosome 17p13 [del(17p)], found in ≈10% of newly diagnosed MM (ND) and at higher prevalence in advanced disease.1, 2, 3, 4, 5 The TP53 gene is located within the minimally deleted region on 17p13, and is thought to confer the adverse risk in a haploinsufficient manner.6 The incidence of TP53 mutations in ND is ≈3% but also increases with disease progression,7, 8 and is associated with shorter survival.9 Although TP53 mutations are uncommon in the absence of del(17p), approximately one third of del(17p) MM patients are reported to have a TP53 mutation, and this increases in refractory disease to more than 50%.8, 10

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