Abstract
Individualizing oncologic treatment by using precision oncology techniques that allow for detection of genomic alterations (GA) has become critical. We present an analysis of comprehensive genomic profiling (CGP) of a large series of high grade serous ovarian carcinoma (HGSOC) patients assayed in a nationwide cancer network. Racial disparities in genomic alterations may assist in better targeting therapies, predicting drug resistance, and potential germline mutations.
312 patients with HGSOC underwent CGP with hybrid capture on tumor tissue for treatment decision-making between 01–2013 to 06–2021. Clinically relevant genomic alterations (CRGA) were reported as targetable marker. Statistical analysis performed with Fisher Exact test.
Median age was 55 years (range, 23-81), 71.2% were White, 16.4% were Black, 3.9% were Hispanic, and 1.3% were Asian. GA were identified in 98.7% (308/312) of these patients. TP53 mutations were present in 286 of 312 patients (91.7%) and interestingly, while not statistically significant (p=0.06) was present in 98% of black women and 89.2% of white women. BRCA1 mutation was present in 14.4% of white women and in 17.6% of black women. BRCA2 mutation was present in 9.9% of white women and 9.8% of black women. Several interesting mutations were identified (Table 1).Table 1Gene/RaceTotal (%) n=312Black (%) n=51White (%) n=222p valueTP53286 (91.7)50 (98.0)198 (89.2)0.06BRCA152 (16.7)9 (17.6)32 (14.4)0.67BRCA227 (8.7)5 (9.8)22 (9.9)1MYC61 (19.6)6 (11.8)43 (19.4)0.23KRAS34 (10.9)10 (19.6)21 (9.5)0.05CCNE138 (12.2)8 (15.7)25 (11.3)0.35NF142 (13.5)5 (9.8)31 (14.0)0.50PIK3CA28 (9.0)4 (7.8)22 (9.9)0.79
In this 312-patient series of women with HGSOC, we note several prominent mutations in the tumors. While not statistically significant, there is a trend of larger number of poorer prognostic mutations in black women including p53, KRAS and CCNE1. Some studies have found the amplification of CCNE1 and mutation of homologous recombination repair genes to be mutually exclusive in HGSOC which may compel us to find other therapeutic interventions than the PARP inhibitors for these patients.