The Role of Centrosomes in Multiple Myeloma - The Centrosome - page 250

Table 15.1 (continued)

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

ILK ILK regulates centrosome clustering and prevents multipolar

divisions (Fielding et al. 2011 )

ILK inhibition leads to apoptosis in HMCL (Wang et al.
2011a )

KRAS The Ras oncogene signals centrosome amplification in mammary

epithelial cells through cyclin D1/Cdk4 and Nek2; KRAS G12D
initiates centrosome amplification in mammary precursor
lesions (Zeng et al. 2010 )

KRAS mutations are present in 6 % of MM cases, and are
significantly associated with shorter overall survival and
progression free survival (Chng et al. 2008 )

LATS2 Aurora A phosphorylates and targets LATS2 to the centrosome

(Toji et al. 2004 ); Cells from Lats2-deficient mice show mitotic
defects associated with centrosome fragmentation
(McPherson et al. 2004 ; Yabuta et al. 2007 )

Homozygous deletion of LATS2 observed in MM (Dickens
et al. 2010 )

MDM2 Forced expression of MDM2 in cells harboring wild-type p53

efficiently induces centrosome amplification (Carroll et al. 1999 )

MDM2 genomic amplification present in MM (Elnenaei et al.
2003 )

MET Constitutive active MET induces supernumerary centrosomes

in vitro (Nam et al. 2010 )

Serum HGF (hepatocyte growth factor; ligand for c-MET)
levels are elevated in MM patients (Seidel et al. 1998 );
MET knockdown/depletion results in decreased MM cell
survival (Phillip et al. 2009 ; Stellrecht et al. 2007 )

NPM1 Probably functions in centrosome pairing (Shinmura et al. 2005 );

NPM controls numeral integrity of centrosomes (Grisendi
et al. 2005 )

NPM1 is overexpressed in hyperdiploid multiple myeloma due
to a gain of chromosome 5 (Weinhold et al. 2010 )

Plk Overexpression of Plk1 in HeLa cells results in extra copies of

centrosomes (Meraldi et al. 2002 )

Plk inhibitor BI 2536 exhibits potent activity against malignant
plasma cells (Stewart et al. 2011 )

p16 INK4a Loss of p16 INK4a generates supernumerary centrosomes through

centriole pair splitting (McDermott et al. 2006 )

p16 methylation observed in MGUS, SMM, and MM;
conflicting results regarding association between p16
methylation status and prognosis (Kramer et al. 2002 ;
Gonzalez-Paz et al. 2007 ; Dib et al. 2007 ; Park et al. 2011 ;
Wong et al. 1998 ; Ribas et al. 2005 ; Mateos et al. 2002 );
hemizygous p16 INK4A deletion reported in MM (Kramer

et al. 2002 )

(continued)