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Table 4.

Mutational spectra of p53 in African American and Caucasian patients in relation to Pro/Pro phenotype

Case No.p53codonNucleotide changeAmino acid changeStructural element affected*Amino acid contactMutation typeExon-conserved area affectedTumors stage at diagnosis
African American patients (17 of 24; 71% of cases with p53 mutations)         
p47 270 TTT>TGT Phe>Cys S10 β sheet Buried Disruptive 8-Cons V III C 
p106 152 CCG>CTG Pro>Leu PE Nondisruptive 5-Outside Cons III C 
p110 153 CCC>CTC Pro>Leu PE Nondisruptive 5-Outside Cons III C 
p132 196 CGA>TGA STOP Truncated Disruptive 6-Cons III IV D 
p138 176 TGC>TAC Cys>Tyr L2 loop Zn binding Nondisruptive 5-Cons III II B 
p146 220 TAT>CAT Tyr>His Buried Nondisruptive 6-Outside Cons III C 
p168 282 CGG>TGG Arg>Trp H2 helix Buried Disruptive 8-Cons V IV D 
p187 213 CGA> TGA STOP Truncated Disruptive 6-Outside Cons I A 
p198 196 CGA>TGA STOP Truncated Disruptive 6-Outside Cons III C 
p222 248 CGG>CAG Arg>Gln L3 loop DNA contact Disruptive 7-Cons IV III C 
p251 258 GAA>GAC Glu>Asp S9 β sheet Buried Nondisruptive 7-Cons IV III C 
p262 273 CGT>CAT Arg>His S10 β sheet DNA contact Nondisruptive 8-Cons V II B 
p276 194 CTT>CGT Leu>Arg L2 loop Buried Disruptive 6-Outside Cons III C 
p283 273 CGT>TGT Arg>Cys S10 β sheet DNA contact Disruptive 8-Cond V IV D 
p285 175 CGC>CAC Arg>His L2 loop Buried Nondisruptive 5-Cons III IV D 
p291 282 CGG>TGG Arg>Trp H2 helix Buried Disruptive 8-Cons V II B 
p401 273 CGT>CTT Arg>Leu S10 β sheet DNA contact Disruptive 8-Cons V III C 
         
Caucasian patients (6 of 17; 35% of cases with p53 mutations)         
P195 175 CGC>CAC Arg>His L2 loop Buried Nondisruptive 5-Cons III II B 
P207 242 TGC>TAC Cys>Tyr L3 loop Zn binding Nondisruptive 7-Cons IV II B 
P243 286 GAA>AAA Glu>Lys H2 helix PE Disruptive 8-Cons V II B 
P252 282 CGG>TGG Arg>Trp H2 helix Buried Disruptive 8-Cons V IVD 
P281 245 GGC>AGC Gly>Ser L3 loop Buried Nondisruptive 7-Cons IV II B 
P302 236 TAC>TGC Tyr>Cys S8 β sheet Buried Nondisruptive 7-Cons IV II B 
Case No.p53codonNucleotide changeAmino acid changeStructural element affected*Amino acid contactMutation typeExon-conserved area affectedTumors stage at diagnosis
African American patients (17 of 24; 71% of cases with p53 mutations)         
p47 270 TTT>TGT Phe>Cys S10 β sheet Buried Disruptive 8-Cons V III C 
p106 152 CCG>CTG Pro>Leu PE Nondisruptive 5-Outside Cons III C 
p110 153 CCC>CTC Pro>Leu PE Nondisruptive 5-Outside Cons III C 
p132 196 CGA>TGA STOP Truncated Disruptive 6-Cons III IV D 
p138 176 TGC>TAC Cys>Tyr L2 loop Zn binding Nondisruptive 5-Cons III II B 
p146 220 TAT>CAT Tyr>His Buried Nondisruptive 6-Outside Cons III C 
p168 282 CGG>TGG Arg>Trp H2 helix Buried Disruptive 8-Cons V IV D 
p187 213 CGA> TGA STOP Truncated Disruptive 6-Outside Cons I A 
p198 196 CGA>TGA STOP Truncated Disruptive 6-Outside Cons III C 
p222 248 CGG>CAG Arg>Gln L3 loop DNA contact Disruptive 7-Cons IV III C 
p251 258 GAA>GAC Glu>Asp S9 β sheet Buried Nondisruptive 7-Cons IV III C 
p262 273 CGT>CAT Arg>His S10 β sheet DNA contact Nondisruptive 8-Cons V II B 
p276 194 CTT>CGT Leu>Arg L2 loop Buried Disruptive 6-Outside Cons III C 
p283 273 CGT>TGT Arg>Cys S10 β sheet DNA contact Disruptive 8-Cond V IV D 
p285 175 CGC>CAC Arg>His L2 loop Buried Nondisruptive 5-Cons III IV D 
p291 282 CGG>TGG Arg>Trp H2 helix Buried Disruptive 8-Cons V II B 
p401 273 CGT>CTT Arg>Leu S10 β sheet DNA contact Disruptive 8-Cons V III C 
         
Caucasian patients (6 of 17; 35% of cases with p53 mutations)         
P195 175 CGC>CAC Arg>His L2 loop Buried Nondisruptive 5-Cons III II B 
P207 242 TGC>TAC Cys>Tyr L3 loop Zn binding Nondisruptive 7-Cons IV II B 
P243 286 GAA>AAA Glu>Lys H2 helix PE Disruptive 8-Cons V II B 
P252 282 CGG>TGG Arg>Trp H2 helix Buried Disruptive 8-Cons V IVD 
P281 245 GGC>AGC Gly>Ser L3 loop Buried Nondisruptive 7-Cons IV II B 
P302 236 TAC>TGC Tyr>Cys S8 β sheet Buried Nondisruptive 7-Cons IV II B 

Abbreviations: Cons, evolutionarily conserved area; Outside cons, outside evolutionarily conserved area. Buried, <15% of DNA binding site surface area exposed. PE, partially exposed (>15 or <50% of DNA binding site surface area exposed); Disruptive, mutation that introduces an amino acid that disrupts the biding site; Nondisruptive, mutation that introduces an amino acid that does not disrupt the binding site.

*

Structural element feature as described in Cho et al. (1994).

Contact features of amino acids with DNA.

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