To determine the prevalence of somatic homologous recombination (HR) gene mutations in uterine serous cancer (USC) and compare these with rates among high-grade serous ovarian cancer (HGSOC).
The American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 12.0 was queried via cBioPortal (http://genie.cbioportal.org). This is a publicly available, multi-institutional database of next-generation sequencing genomic profiles of tumor samples. Mutation frequencies for 8 homologous recombination deficiency (HRD) genes are reported and compared between uterine serous cancer (USC) and high-grade serous ovarian cancer (HGSOC) samples using chi-squared or Fischer’s exact tests. The threshold used for statistical significance was a two-sided alpha of 0.05.
| Mutation frequency among USC | Mutation frequency among HGSOC | P-value | |
|---|---|---|---|
| BRCA1 | 12/776, 1.5% | 313/3125, 10.0% | p<0.001 |
| BRCA2 | 40/776, 5.2% | 218/3125, 7.0% | p<0.001 |
| BRIP1 | 4/752, 0.5% | 57/2974, 1.9% | p<0.01 |
| CHEK2 | 6/768, 0.8% | 19/3040, 0.6% | 0.82 |
| BARD1 | 12/664, 1.8% | 55/2615, 2.1% | 0.74 |
| RAD51C | 3/671, 0.4% | 27/2663, 1.0% | 0.25 |
| RAD51D | 4/671, 0.6% | 24/2658, 0.9% | 0.59 |
| PALB2 | 12/766, 1.6% | 37/3045, 1.2% | 0.58 |
Among 844 USC samples, the most prevalent somatic HR gene mutations were BRCA2 (5.2%), BARD1 (1.8%), PALB2 (1.6%) and BRCA1 (1.5%). When compared to 3304 HGSOC samples, higher HR gene mutation frequencies among HGSOC were only found for BRCA1 (10.0% vs 1.5%, p<0.001), BRCA2 (7.0% vs 5.2%, p<0.001) and BRIP1 (1.9% vs 0.5%, p<0.01); however, there was no difference between HGSOC and USC samples in mutation frequencies of BARD1, CHEK2, RAD51C, RAD51D or PALB2 (Table 1).
Genomic profiling of USC tumor samples demonstrates a substantial rate of somatic gene mutations conferring HR deficiency, with rates for most HR gene mutations similar to those found among HGSOC samples. This demonstrates the need for genetically targeted clinical trials of poly-ADP ribose polymerase (PARP) inhibitors in patients with USC, and further research into the germline genetic profile of these patients to establish if this rare uterine cancer could be a phenotype of the hereditary breast and ovarian cancer syndrome.