Introduction/Background We aimed to characterize the mutational landscape of uterine sarcoma.

Methodology Data were extracted from the American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.1 via cBioPortal (http://genie.cbioportal.org). We queried this database for uterine sarcoma samples and analyzed frequencies of pathogenic gene variants (PGVs) for which targeted therapies are currently available or in clinical trials for other cancer types. These included PGVs associated with homologous recombination deficiency (HRD): ATM, ARID1A, ATRX, BRCA1, BRCA2, BARD1, BRIP1, BLM, BAP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN; PGVs associated with the MAP-kinase signaling pathway: BRAF (V600E), KRAS, NRAS, EIF1AX; PGVs associated with mismatch repair (MMR): MSH2, MSH3, MSH6, MLH1, MLH3, PMS2, EPCAM; PGVs in other genes: PTEN, PIK3CA, MTOR, CDKN2A, CDKN2B, and ERBB2 (amplification).

Results A total of 704 uterine sarcoma tumor samples from 680 patients were included for analysis. At least one somatic PGV was observed in an HRD associated gene in 27.8% (196/704) of all tumors, with the most common PGVs observed in ATRX (109/645, 16.9%), BRCA2 (27/652, 4.1%) and RAD51B (16/435, 3.7%). At least one somatic PGV was observed in an MMR associated gene in 3.0% (21/704) of all tumors, with the most common PGVs observed in MSH6 (6/648, 0.9%) and MSH2 (5/633, 0.8%). At least one somatic PGV was observed in a MAP-Kinase associated gene in 2.8% (20/704) of all tumors, with the most common PGVs observed in KRAS (14/680, 2.1%). Highest frequencies of other targetable PGVs were observed in PTEN (89/677, 13.1%) and PIK3CA (16/680, 2.4%).

Conclusion The high rate of PGVs in HRD genes and PTEN in uterine sarcoma tumor samples suggests the need for clinical trials evaluating the efficacy of genetically targeted therapies for this patient population.

Disclosures No relevant conflict of interest disclosures for any of the co-authors.