Table 1.
PPM1D protein truncating variants with time of blood collection for DNA
| Summary | Mutation frequency, No. (%) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Control patients (n = 3431) | 1 (0.03) | |||||||||||
| All case patients (n = 3236) | 12 (0.37)† | |||||||||||
| Pretreatment case patients (n = 1384)‡ | 0 (0)|| | |||||||||||
| Post-treatment case patients (n = 1827)§ | 12 (0.66)¶ | |||||||||||
| All case patients | Alternate allele freq (MPS data) | Average 18 gene alternate allele freq# | Age at diagnosis, mean, y | Time to blood draw from diagnosis (pretreatment)‡, mean | Time to blood draw from diagnosis (post-treatment)§, mean | |||||||
| Carrier case patients (n = 12) | 27.6 | 49.4 | 59.8 | NA | 1234 d | |||||||
| Noncarrier case patients (n = 3199) | NA | 49.8 | 59.3 | 2 d | 847 d | |||||||
| Individuals (study site) | Alternate allele freq (MPS data) | Average 18 gene alternate allele freq# (range) | Age at diagnosis, y | Histology†† | Time to blood draw from diagnosis (post-treatment)§ | DNA change | Predicted protein change | |||||
| Case 1 (GRR) | 37.8 | 51.7 (38.3–66.8) | 55 | Serous | 3682 d | c.1280G>A | p.W427* | |||||
| Case 2 (MAY)‡‡ | 45.3 | 49.2 (21.4–80.0) | 86 | HGS | 65 d | c.1349delT | p.L450* | |||||
| Case 3 (AOC) | 40.3 | 49.2 (32.4–75.1) | 60 | HGS | 576 d | c.1384C>T | p.Q462* | |||||
| Case 4 (SEA) | 31.8 | 50.8 (44.6–68.9) | 61 | LGS | 314 d | c.1423G>T | p.E475* | |||||
| Case 5 (SEA) | 42.3 | 52.3 (45.7–66.9) | 65 | LGS | 875 d | c.1535delA | p.N512fs | |||||
| Case 6 (UKO) | 25.8 | 49.4 (42.3–53.0) | 55 | HGS | 1185 d | c.1608delG | p.R536fs | |||||
| Case 7 (SEA) | 19.4 | 52.9 (44.2–69.0) | 67 | HGS | 847 d | c.1337delC | p.S446* | |||||
| Case 8 (SEA) | 17.3 | 45.0 (18.1–77.0) | 66 | LGS | 540 d | c.1339_1342delGAGA | p.E447fs | |||||
| Case 9 (GRR) | 14.6 | 48.3 (27.0–68.4) | 64 | HGS | 674 d | c.1403C>G | p.S468* | |||||
| Case 10 (SEA) | 17.8 | 50.5 (40.5–62.3) | 60 | LGS | 849 d | c.1412delC | p.P471fs | |||||
| Case 11 (GRR) | 18.4 | 45.8 (30.0–55.1) | 21 | LGS | 4625 d | c.1535delA | p.N512fs | |||||
| Case 12 (SEA) | 20.1 | 48.0 (25.0–75.0) | 58 | HGS | 581 d | c.1579G>T | p.E527* | |||||
| Control 1 (MAY)§§ | 14.7 | 46.7 (19.0–54.1) | Prior breast cancer | 6 y after start Tamoxifen | c.1434C>A | p.C478* | ||||||
* Indicates protein termination. Order of variants is sorted by those with alternate allele frequency higher than 25% and then those 25% or lower and within each group sorted by nucleotide position. AOC = Australian Ovarian Cancer Study; GRR = Gilda Radner Familial Ovarian Cancer Registry; HGS = high-grade serous; LGS = low-grade serous; MAY = Mayo Clinic Ovarian Cancer Study; MPS = massively parallel sequencing; SEA = SEARCH; UKO = United Kingdom Ovarian Cancer Population Study.
† Carrier frequency, all case patients vs control patients, P = .001.
‡ Case patients in which blood for genetic analyses was drawn at or no later up to 14 days after diagnosis (ie, pretreatment).
§ Case patients in which blood for genetic analyses was 14 or more days after diagnosis (ie, post-treatment); 25 case patients had unknown time between diagnosis and blood for DNA sample.
|| Carrier frequency, post-treatment case patients vs pretreatment case patients, P = .002.
¶ Carrier frequency, post-treatment case patients vs control patients, P < .001. Fisher’s exact test, two-tailed P values.
# Average alternate allele frequency for all other variants for each sample from MPS data and range.
†† Reported histology for case patients: serous (grade not reported), HGS (high-grade serous), LGS (low-grade serous).
‡‡ The variant in this individual did not show strong evidence of being mosaic by Sanger sequencing or pyrosequencing.
§§ This control patient had a prior history of breast cancer.