Table 2.
CpG transition strand asymmetry in the p53 gene: Codon resolution
| Codon | Germ line
single
|
Tumor single
|
Tumor multiple†
|
|
|---|---|---|---|---|
| NC → T/NG → A* transitions | NC → T/NG → A transitions | NC → T/NG → A transitions (I) | NC → T/NG → A transitions (II) | |
| Transactivation domain | ||||
| 10–11 GTCGAG | — | — | 0/1 | — |
| 30–31 AACGTT | — | — | 0/1 | — |
| 36 CCG | — | — | 0/3 | — |
| 47 CCG | — | 2/0 | — | — |
| 82 CCG | 1/0 | — | — | — |
| Central domain | ||||
| 110 CGT | — | 3/0 | — | — |
| 125 ACG | — | 2/0 | 0/1 | — |
| 152 CCG | 1/0 | 15/0 | 6/6 | 4/6 |
| 153–154 CCCGGC | — | 0/2 | 3/1 | — |
| 156 CGC | — | 2/2 | — | — |
| 156–157 CGCGTC | — | 0/4 | 0/2 | — |
| 158 CGC | — | 5/23 | 1/3 | 0/3 |
| 158–159 CGCGCC | — | 0/3 | 2/1 | — |
| 170 ACG | — | 2/0 | 2/2 | 1/2 |
| 175 CGC | 0/8 | 4/284 | 6/16‡ | 2/16‡ |
| 181 CGC | 1/1 | 8/12 | 0/2 | — |
| 196 CGA | — | 61/1 | 6/2 | 3/2 |
| 202 CGT | — | 1/2 | 1/0 | — |
| 213 CGA | 2/0 | 72/8 | 7/6‡ | 4/6 |
| 222 CCG | — | — | 1/0 | — |
| 244–245 GGCGGC | 0/6 | 0/102 | 0/14 | — |
| 248 CGG | 11/8 | 189/234 | 12/22 | 2/22‡ |
| 267 CGG | 0/1 | 8/1 | 1/1 | — |
| 273 CGT | 4/4 | 190/224 | 7/20 | 3/20‡ |
| 282 CGG | 6/0 | 141/8 | 15/6‡ | 8/6‡ |
| 283 CGC | — | 6/2 | 1/1 | — |
| 290 CGC | — | 3/2 | 0/4 | — |
| 297–298 CACGAG | — | — | 1/1 | — |
| Tetramerization domain | ||||
| 306 CGA | 1/0 | 22/0 | 1/0 | — |
| 337 CGC | 1/1 | 4/0 | — | — |
| 342 CGA | — | 25/0 | 1/1 | — |
NC→T/NG→A is a ratio of putative CpG→TpG deamination-induced transitions on the nontranscribed strand to the ones that occurred on the transcribed strand. Five hotspot CpG sites are shown in boldface type.
Column (I) shows total NC→T at each CpG, while in column (II) the C→Ts that are hitchhiking parts of the heterostrand doublets (C→T G→A) are excluded. This allows testing the Td vs. Rd origin of tumor-driving p53 mutations by comparing the strand asymmetry in germ–line/singlet, somatic/singlet, and somatic/multiplet groups.
Based on the nominal cross tabulation, various statistical tests were performed to ascertain whether the observed differences of the NC→T/NG→A value between the three groups were statistically significant. The confidence levels of more than 99% were obtained for codons 175, 213, 248, 273, and 282, thus indicating nonrandomness of the differences. Although the remaining codons also fit the Td hypothesis, they were not statistically tested because of small sample size.