Table 1.
Germline and somatic BRCA1/2 pathogenic variants by age and familial situation with germline miss rates and somatic-to-germline ratios.
| Non-familial OC (low familial risk) | Familial OC | Combined total | HGSC | CCC | EOC | Carcinosarcoma | Other | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (years) | Total | ||||||||||||
| <30 | 30–49 | 50–59 | 60–69 | 70 + | |||||||||
| Full germline BRCA1/2 testing database (N = 1755) | |||||||||||||
| Germline BRCA1/2 tested (no.) | 18 | 199 | 319 | 325 | 271 | 1114 | 641 | 1755 | 1512 | 61 | 108 | 23 | 51d |
| gBRCA1/2 wild-type (no.) | 18 | 177 | 285 | 297 | 263 | 1022 | 396 | 1418 | 1197 | 55 | 97 | 18 | 51d |
| gBRCA1 PV (no.) | 0 | 12 | 19 | 9 | 0 | 40 | 160 | 200 | 188 | 4 | 7 | 1 | 0 |
| %a | 0.0% | 6.0% | 6.0% | 2.8% | 0.0% | 3.6% | 25.0% | 11.4% | 12.4% | 6.6% | 6.5% | 4.3% | 0.0% |
| gBRCA2 PV (no.) | 0 | 10 | 15 | 19 | 8 | 52 | 85 | 137 | 127 | 2 | 4 | 4 | 0 |
| %a | 0.0% | 5.6% | 5.3% | 6.4% | 3.0% | 5.1% | 21.5% | 9.7% | 10.6% | 3.6% | 4.1% | 22.2% | 0.0% |
| Combined gBRCA1/2 PV (no.) | 0 | 22 | 34 | 28 | 8 | 92 | 245 | 337 | 315 | 6 | 11 | 5 | 0 |
| % Combined gBRCA1/2 PVa | 0.0% | 11.1% | 10.7% | 8.6% | 3.0% | 8.3% | 38.2% | 19.2% | 20.8% | 9.8% | 10.2% | 21.7% | 0.0% |
| Successful paired tumour and germline BRCA1/2 testing cohort (N = 388) | |||||||||||||
| BRCA1/2 tested (no.) | 0 | 42 | 82 | 107 | 112 | 343 | 45 | 388 | 361 | 9 | 15 | 1 | 2 |
| gBRCA1/2 PV confirmed (no.) | 0 | 5 | 3 | 6 | 1 | 15 | 23 | 38 | 32 | 1 | 3 | 0 | 0 |
| gBRCA1/2 wild-type (no.) | 0 | 37 | 79 | 101 | 111 | 328 | 22 | 350 | 327 | 8 | 12 | 1 | 2 |
| gBRCA1/2 PV missed in tumour DNA (no.) | 0 | 0 | 0 | 2b | 0 | 2b | 0 | 2b | 2b | 0 | 0 | 0 | 0 |
| % gBRCA1/2 PV Missed | 0.0% | 0.0% | 0.0% | 33.3% | 0.0% | 13.3% | 0.0% | 5.3% | 5.9% | 0.0% | 0.0% | 0.0% | 0.0% |
| sBRCA1 PV (no.) | 0 | 3 | 3 | 6 | 6 | 18 | 0 | 18 | 18 | 0 | 0 | 0 | 0 |
| %c | 0.0% | 8.1% | 3.8% | 5.9% | 5.4% | 5.5% | 0.0% | 5.1% | 5.5% | 0.0% | 0.0% | 0.0% | 0.0% |
| sBRCA2 PV (no.) | 0 | 1 | 1 | 3 | 11 | 16 | 0 | 16 | 15 | 1 | 0 | 0 | 0 |
| %c | 0.0% | 2.7% | 1.3% | 3.0% | 9.9% | 4.9% | 0.0% | 4.6% | 4.6% | 12.5% | 0.0% | 0.0% | 0.0% |
| Combined sBRCA1/2 PV (no.) | 0 | 4 | 4 | 9 | 17 | 34 | 0 | 34 | 33 | 1 | 0 | 0 | 0 |
| % Combined sBRCA1/2 PVc | 0.0% | 10.8% | 5.1% | 8.9% | 15.3% | 10.4% | 0.0% | 9.7% | 10.1% | 12.5% | 0.0% | 0.0% | 0.0% |
| sBRCA-to-gBRCA ratio | 0.0 | 1.0 | 0.5 | 1.0 | 5.2 | 1.3 | 0.0 | 0.5 | 0.5 | 1.3 | 0.0 | 0.0 | 0.0 |
| Missed rate gBRCA1/2 CNVs | 0.0% | 1.3% | 1.2% | 0.7% | 0.4% | 0.9% | 5.0% | 2.4% | 2.7% | 1.8% | 1.3% | 0.9% | 0.0% |
CCC clear cell carcinoma, CNVs copy-number variants, EOC endometrioid ovarian carcinoma, gBRCA germline BRCA1/2, HGSC high-grade serous carcinoma, no. number, OC ovarian cancer, PV pathogenic variant, sBRCA somatic BRCA1/2.
aThe denominator is the number of cases tested for germline BRCA1/2 pathogenic variants.
bTwo cases of non-mucinous epithelial ovarian cancers had a copy-number variant detected in germline DNA but not in tumour DNA.
cThe denominator is the number of cases tested for tumour BRCA1/2 pathogenic variants with confirmed germline BRCA1/2 wild-type.
dIncludes n = 11 and n = 2 low-grade serous carcinoma cases who underwent blood (germline) and tumour (somatic) testing, respectively, as well as adenocarcinoma otherwise specified (NOS).