The Role of Centrosomes in Multiple Myeloma - The Centrosome - page 251

Table 15.1 (continued)

Gene Known role in centrosome function or regulation of centrosome number Role in myeloma oncogenesis

p18 No direct link to centrosome regulation documented, although

it inhibits CDK4/CDK6 (Hirai et al. 1995 )

Prevalence of bi-allelic p18 deletion in MM is about 2 %;
exogenous p18 expression inhibits growth of HMCL with
low/absent endogenous p18 expression (Dib et al. 2006 )

p27 p27 suppresses centrosome amplification after DNA damage

(Sugihara et al. 2006 )

Low p27 is an adverse prognostic factor in patients with MM
(Filipits et al. 2003 )

RAD51 Expression of dominant-negative RAD51 and conditional repression

of RAD51 leads to centrosome amplification (Bertrand et al.
2003 ); reduced expression or loss of RAD51B, RAD51C,
RAD51D, XRCC2, and XRCC3 all induce centrosome
amplification (Renglin et al. 2007 ; Smiraldo et al. 2005 ;
Griffin et al. 2000 ; Date et al. 2006 )

One study comparing MM cells in one patient with normal
plasma cells in her identical twin reported downregulation
of RAD51 in MM cells by gene expression analysis
(Munshi et al. 2004 )

Rb Inactivation of Rb by expression of E7 results in centrosome

amplification (Duensing et al. 2000 ); conditional Rb loss
in mice results in centrosome amplification (Iovino
et al. 2006 ; Balsitis et al. 2003 )

Heterozygous deletion of Rb present in MM (Juge-Morineau
et al. 1997 ; Kramer et al. 2002 )

RHAMM RHAMM localizes to the centrosome (Maxwell et al. 2003 ) RHAMM overexpression in vitro in HMCL results in

centrosomal defects (Maxwell et al. 2005 )

TP53 p53-deficient mice show a high frequency of centrosome

amplification (Fukasawa and Wiener 1997 ; Fukasawa et al.
1996 ); efficient centrosome reduplication occurs only when p53
is mutated or lost (Tarapore et al. 2001 ); The absence of p53
favors the accumulation of cells with extra centrosomes
(Meraldi et al. 2002 )

TP53 mutation prevalence 0-40 % in MM (Fonseca et al.
2004 ; Chng et al. 2007 ); TP53 mutations associated with
very poor survival (Chng et al. 2007 )