Table 1.

The TP53 status of the cell lines with response to GSK461364A determined by a compound washout/outgrowth assay

TissueCell lineGI50ResponseTP53 statusTP53 mutationTP53 mutation dominant negativeReported occurrence
LungMV5226SensitiveMutatedG818AYes754
LungNCI-H824SensitiveNullNull
PancreasCapan-2148SensitiveNullNull
LungNCI-H15715SensitiveNullNull
LungNCI-H5226SensitiveNullNull
BreastMDA-MB-4687SensitiveMutatedG818AYes754
ColonColo2057SensitiveMutated26bp deletion/TA insertion at bp 308-333Frame shift
LungNCI-H59640SensitiveMutatedG733TYes
BreastSKBR36SensitiveMutatedG524AYes1,128
BreastMCF77SensitiveWild Type
MelanomaA4317SensitiveMutatedG818AYes754
MelanomaSKMEL310SensitiveMutated26 bp deletion/TA insertion at bp 308-333Frame shift
BreastMDA-MB-4536SensitiveNullNull
ColonLovo12SensitiveWild-type
BreastMDA-MB-23113SensitiveMutatedG839AYes76
StomachNCI-N876SensitiveMutatedG743AYes859
OvaryOVCAR88SensitiveMutated21bp del (376-396)Del
PancreasPL4522SensitiveMutatedT764ANA6
SarcomaSaos-26SensitiveNullNull
ColonSW6204SensitiveMutatedG818A, C925TYes754
PancreasASPC18SensitiveNullNull
BreastBT54923SensitiveMutatedG108A, G747CYes369
LungNCI-H3228SensitiveMutatedG743TYes112
PancreasMiaPaCa16SensitiveMutatedC742TYes700
BreastZR-75-146SensitiveWild-type
LungNCI-H129933ResistantWild-type
Normal-SkinHFF7,011ResistantWild-type
LungNCI-H46010ResistantWild-type
LungA54912ResistantWild-type
Head and neckHN510ResistantMutatedT712ANA15
CervixHeLa5ResistantWild-type
ColonHCT1168ResistantWild-type
ProstateLNCap6ResistantWild-type
Normal-VeinHuVec70ResistantWild-type
MelanomaMALME3M9ResistantMutated (hetero)T434G/T, G435G/TNA9
MelanomaSKMEL528ResistantWild-type
MelanomaSKMEL2819ResistantMutatedT434G, G435TNA9
MelanomaA375PF1124ResistantWild-type
ProstatePC310ResistantNullC413delNull
ColonDLD-110ResistantMutated (hetero)C722C/TYes99
RenalA704183ResistantWild-type
RenalSW1564,663ResistantWild-type
LungNCI-H727121ResistantMutated (added 3AA)Insertion 9 bps: 497-505NANever reported

NOTE: The TP53 status for each cell line was determined based on three sets of data: COSMIC database (27), direct sequencing of cDNA or genomic DNA, and level of TP53 mRNA expression from the Affymetrix expression array analysis (Supplementary Table S3; ref. 20). The dominant-negative status was sourced from the IARC (28) database and the reported occurrence was based on the Universal Mutation Database (32). GI50s from a 72-h proliferation assay under constant drug exposure are also listed.

    Abbreviation: HFF, human foreskin fibroblasts.