Abstract 4258: Racial and ethnic differences in the mutational landscape of low-grade serous ovarian cancer
Authors: Ahsan Muhammad Danyal , Webster Emily M. , Levi Sarah R. , Nguyen Natalie T. , Cubillos-Ruiz Juan R. , Cantillo Evelyn , Chapman-Davis Eloise , Frey Melissa K. , Holcomb Kevin 
Published: April 2023

Objective To characterize the mutational landscape of low grade serous ovarian cancer (LGSOC) with racial/ethnic stratification.

Methods The AACR Project GENIE database version 12.0 was queried via cBioPortal (http://genie.cbioportal.org) for low-grade serous ovarian cancer (LGSOC) samples. This is a publicly available, de-identified, multi-institutional database of next-generation sequencing genomic profiling results for tumor samples. Mutation frequencies for 9 homologous recombination deficiency (HRD) genes, 4 MAP-Kinase (MAP-K) pathway genes and 6 mismatch-repair (MMR) deficiency genes were reported and compared between racial/ethnic groups using chi-squared or Fischer’s exact tests. The threshold used for statistical significance was a two-sided alpha of 0.05.

Results Among 317 tumor samples of LGSOC, there were high rates of MAP-K pathway gene mutations but low rates of HRD, MMR and TP53 gene mutations (Table 1). Non-Hispanic Black patients had significantly higher rates of KRAS mutations compared to non-Hispanic White patients (6/7, 86% vs 48/178, 27%, p&lt;0.01). There was no difference in KRAS mutation frequency among Asian (6/17, 35%), Hispanic (7/24, 29%) and Native American (2/2, 100%) patients when compared to non-Hispanic White patients. BRAF mutations were less common compared to KRAS mutations (32/317, 10%), with no racial/ethnic differences in mutation frequency.

Conclusion High rates of MAP-K pathway mutations in LGSOC support development and trials of drugs targeting this pathway, such as MEK protein inhibitors. Furthermore, prior literature has demonstrated the prognostic advantage of KRAS and BRAF mutations in LGSOC as well as the association of KRAS mutations with progression of serous borderline tumors to LGSOC. These racial/ethnic differences in frequencies of these mutations are thus hypothesis generating for clinical research to evaluate the impact of race/ethnicity on the development and prognosis of this rare ovarian cancer.

Mutation frequencies of HR, MAP-kinase, MMR and TP53 genes in low-grade serous ovarian cancer Gene No. of samples with ≥1 mutation No. of samples profiled for mutation Mutation frequency BRCA1 3 287 1.05 BRCA2 7 287 2.44 BRIP1 5 271 1.85 CHEK2 2 278 0.72 BARD1 2 239 0.84 RAD51B - - - RAD51C - - - RAD51D 2 246 0.81 PALB2 2 279 0.72 KRAS 93 317 29.34 NRAS 29 317 9.15 BRAF 32 317 10.09 EIF1AX 14 144 9.72 MSH2 3 275 1.09 MSH3 1 113 0.88 MSH6 6 286 2.10 MLH1 1 317 0.32 MLH3 3 96 3.13 PMS2 1 270 0.37 TP53 12 317 3.79

Citation Format: Muhammad Danyal Ahsan, Emily M. Webster, Sarah R. Levi, Natalie T. Nguyen, Juan R. Cubillos-Ruiz, Evelyn Cantillo, Eloise Chapman-Davis, Melissa K. Frey, Kevin Holcomb. Racial and ethnic differences in the mutational landscape of low-grade serous ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4258.