▁the ▁expression ▁of ▁two ▁or ▁more ▁gen es ▁leads ▁to ▁cell ▁death , ▁whereas ▁a ▁def ic iency ▁in ▁only ▁one ▁of ▁these ▁gen es ▁does ▁not . ▁The ▁def ic ien cies ▁can ▁arise ▁through ▁mut ation , ▁ep igen etic ▁alter ation ▁or ▁by ▁in hib ition ▁of ▁a ▁gene ' s ▁expression . ▁ ▁Ir in ot ec an ▁in activ ation ▁of ▁T OP 1 ▁appears ▁to ▁be ▁synth et ically ▁le th al ▁in ▁combination ▁with ▁def ic ien cies ▁in ▁expression ▁of ▁some ▁specific ▁DNA ▁repair ▁gen es . ▁ ▁Ir in ot ec an ▁in activ ation ▁of ▁T OP 1 ▁was ▁synth et ically ▁le th al ▁with ▁def ic ient ▁expression ▁of ▁the ▁DNA ▁repair ▁W R N ▁gene ▁in ▁patients ▁with ▁colon ▁cancer . ▁ ▁In ▁a ▁ 2 0 0 6 ▁study , ▁ 4 5 ▁patients ▁had ▁colon ic ▁tum ors ▁with ▁hyper m eth yl ated ▁W R N ▁gene ▁prom ot ers ▁( sil enced ▁W R N ▁expression ), ▁and ▁ 4 3 ▁patients ▁had ▁tum ors ▁with ▁un m eth yl ated ▁W R N ▁gene ▁prom ot ers , ▁so ▁that ▁W R N ▁protein ▁expression ▁was ▁high . ▁ ▁Ir in ot ec an ▁was ▁more ▁strongly ▁benef icial ▁for ▁patients ▁with ▁hyper m eth yl ated ▁W R N ▁prom ot ers ▁( 3 9 . 4 ▁months ▁surv ival ) ▁than ▁for ▁those ▁with ▁un m eth yl ated ▁W R N ▁prom