Table 2. Tumor-specific variants constructed and analyzed in a yeast deletion background.
| Nucleotide mutation | Amino acid mutation | Zygosity | Amino acid conserved in yeast | PredictSNP (confidence) | No drug | 0.01% MMS | 100 mM HU | |
|---|---|---|---|---|---|---|---|---|
| hLIG1 | 179C > T | A60V | Unknown | No | Neutral (83%) | 0.56 ± 0.06*** | 0.50 ± 0.05 | 0.38 ± 0.03* |
| 421A > G | S141G | Heterozygous | Yes | Neutral (75%) | 0.45 ± 0.03*** | 0.50 ± 0.07 | 0.25 ± 0.05* | |
| 454A > G | K152E | Heterozygous | Yes | Neutral (83%) | 0.52 ± 0.06*** | 0.98 ± 0.06*** | 0.46 ± 0.03 | |
| 455A > G | K152R | Heterozygous | Yes | Neutral (83%) | 0.50 ± 0.05*** | 0.50 ± 0.06 | 0.23 ± 0.01*** | |
| 457G > A | E153K | Heterozygous | No | Neutral (83%) | 0.60 ± 0.12*** | 0.44 ± 0.06 | 0.30 ± 0.07** | |
| 488G > A | S163N | Unknown | No | Neutral (83%) | 0.60 ± 0.12*** | 0.49 ± 0.05 | 0.23 ± 0.06*** | |
| 664C > T | R222C | Heterozygous | No | Neutral (63%) | 0.35 ± 0.01*** | 0.23 ± 0.01*** | 0.21 ± 0.02*** | |
| 1045G > A | V349M | Unknown | No | Neutral (60%) | 0.47 ± 0.03*** | 0.59 ± 0.04* | 0.29 ± 0.05* | |
| 1120G > A | A374T | Unknown | No | Neutral (83%) | 0.71 ± 0.03*** | 0.71 ± 0.06 | 0.51 ± 0.06** | |
| 1184C > A | P395Q | Unknown | No | Neutral (83%) | 0.63 ± 0.05*** | 0.48 ± 0.04** | 0.44 ± 0.04* | |
| 1502T > C | M501T | Unknown | No | Neutral (83%) | 0.61 ± 0.06*** | 0.34 ± 0.01*** | 0.46 ± 0.03* | |
| 1835C > T | S612L | Heterozygous | No | Neutral (74%) | 0.49 ± 0.04*** | 0.33 ± 0.02*** | 0.42 ± 0.04 | |
| 1969T > G | L657V | Heterozygous | Yes | Neutral (83%) | 0.71 ± 0.08*** | 0.70 ± 0.10 | 0.44 ± 0.04** | |
| 2290G > A | A764T | Unknown | Yes | Deleterious (87%) | 0.73 ± 0.09*** | 0.30 ± 0.02*** | 0.61 ± 0.04 | |
| 2353G > A | E785K | Unknown | No | Neutral (75%) | 0.59 ± 0.07*** | 0.52 ± 0.05 | 0.56 ± 0.09 | |
| 2446G > A | V816M | Unknown | No | Neutral (74%) | 0.70 ± 0.06*** | 0.36 ± 0.01*** | 0.47 ± 0.04* | |
| hSSRP1 | 97A > G | K33E | Heterozygous | Yes | Deleterious (87%) | 1.02 ± 0.12 | 0.70 ± 0.08 | 0.95 ± 0.12 |
| 566C > T | A189V | Heterozygous | Yes | Deleterious (72%) | 0.69 ± 0.11** | 0.35 ± 0.03 | 0.79 ± 0.05 | |
| 626C > T | T209I | Unknown | Yes | Deleterious (61%) | 1.09 ± 0.14 | 0.68 ± 0.07* | 1.00 ± 0.12 | |
| 682A > G | K228E | Heterozygous | Yes | Deleterious (87%) | Non-functional | n/d | n/d | |
| 970C > T | R324C | Heterozygous | Yes | Neutral (60%) | 1.00 ± 0.06 | 0.80 ± 0.18 | 0.97 ± 0.10 | |
| 1108C > T | R370C | Heterozygous | No | Deleterious (65%) | 1.05 ± 0.11 | 0.67 ± 0.06* | 0.97 ± 0.17 | |
| 1306C > T | P436S | Heterozygous | No | Neutral (83%) | 0.94 ± 0.05 | 0.81 ± 0.10 | 1.01 ± 0.11 | |
| 1441T > C | S481P | Unknown | No | Deleterious (61%) | Non-functional | n/d | n/d | |
| 1493A > G | N498S | Heterozygous | No | Neutral (74%) | 1.05 ± 0.06 | 0.70 ± 0.04* | 1.08 ± 0.08 | |
| 1723A > G | T575A | Heterozygous | No | Neutral (83%) | 1.02 ± 0.06 | 0.76 ± 0.04* | 1.22 ± 0.13 | |
| 1724C > T | T575M | Unknown | No | Neutral (60%) | 1.02 ± 0.05 | 0.78 ± 0.08* | 1.07 ± 0.10 | |
| 1950G > T | K650N | Unknown | No | Neutral (83%) | 1.07 ± 0.16 | 0.82 ± 0.03 | 1.22 ± 0.03 | |
| hPPP1CA | 428G > A | R143H | Heterozygous | Yes | Deleterious (87%) | 0.69 ± 0.08 | 0.72 ± 0.09 | 0.67 ± 0.03 |
| 815A > G | Y272C | Heterozygous | Yes | Deleterious (87%) | Non-functional | n/d | n/d | |
| hPPP1CC | 348G > T | E116D | Unknown | Yes | Neutral (75%) | 0.57 ± 0.11** | 0.24 ± 0.03* | 0.33 ± 0.01* |
| 559C > T | R187W | Unknown | Yes | Deleterious (87%) | 0.05 ± 0.01*** | 0.05 ± 0.01 | 0.02 ± 0.01* | |
| 601C > T | L201F | Heterozygous | Yes | Deleterious (51%) | 1.48 ± 0.18* | 1.09 ± 0.24 | 1.10 ± 0.11 | |
| 610C > A | L204I | Unknown | Yes | Neutral (63%) | 0.97 ± 0.10 | 0.89 ± 0.22 | 1.07 ± 0.14 | |
| 866T > G | L289R | Heterozygous | Yes | Deleterious (87%) | Nonfunctional | n/d | n/d |
Strain fitness for each allele is expressed as a ratio relative to the yeast strain expressing the wild-type allele grown in the same plate in the same media condition. For “no drug” condition, significance was calculated compared to the wild-type allele grown in the same plate to assess impact of missense mutation on strain fitness. For “drug” condition, significance was calculated compared to the same allele in the no drug condition grown in the same plate to assess impact of drug on strain fitness. Alleles were defined as nonfunctional based on inability to complement the corresponding deletion mutant yeast strain. Strain fitness values that were not determined are indicated (n/d). *P < 0.01, **P < 0.001, ***P < 0.0001.