Implications of Heterogeneity in Multiple Myeloma

Table 5

Driver mutations that may be responsible for clonal evolution in MM.

Affected gene	Type of mutation	Normal function	Postulated role in disease evolution	Study
AFF1	Damaging	Histone methylation	Driver of Myelomagenesis; (found at all disease time points)	Egan et al. 2012 [61]
RUNX2	Inactivating	Regulates osteopontin a bone matrix glycoprotein involved in cell survival	HR SMM to MM	Walker et al. 2014 [64]
BRCA2	Disrupted due to t(13; 21)	DNA repair	HR SMM to MM	Walker et al. 2014 [64]
UNC5D	Inactivating	Induces apoptosis, regulated by p53	HR SMM to MM	Walker et al. 2014 [64]
ZKSCAN3	Truncating	Possible effects on VEGF	PCL transformation	Egan et al. 2012 [61]
Rb1	Truncating	Key tumour suppressor gene	PCL transformation	Egan et al. 2012 [61]

VEGF = Vascular endothelial growth factor, PCL = Plasma cell leukaemia, and HR SMM = High risk smouldering multiple myeloma.