133P ARID1A-mutated cancers: New prospectives for treatment of a subgroup of gynecological cancer

ARID1A encodes a key component of the SWI–SNF chromatin remodeling complex, participating in control PI3K/AKT/mTOR pathway. No data are available for patient populations whose tumors harbor multiple mutations. A variety compounds being tested ARID1A-altered cancers, without any drug approval so far. Molecular and clinical characteristics patients evaluated at Phase I Unit Fondazione Policlinico Gemelli harboring least one alteration were collected. Clinical retrieved from hospital records. analysis was performed by FoundationOne on tissue (primary diagnosis or relapsed tissue) blood. Among 207 that received molecular our site, 19 (9.1%) had pathogenic ARID1A: 15 (79%) alterations solid tissue, 4 (21%) liquid biopsy. Half archival (8/15, 53%) primary diagnosis, others disease. prevalent ovarian cancer (clear cell histotype, 5/19, 26%) endometrial (endometrioid subtype, 5/19=26%), followed cervical (10.5%), colon (10.5%) breast (luminal type) (10.5%). The most frequent co-occurent were: TP53 (8/19=42%), PIK3CA PTEN (6/19=31.5%), CTNNB1 (4/19=21%), ASXL1 MLL2 (4/19=21%). common Q372fs*19 (3/19=16%), identified only both alone combination with another mutation ARID1A. Microsatellite instability status detected 26% (5/19) samples; median value TMB 7.57 mut/MB. Double 5/19 (26%) patients; majority them (4/5, 80%) carcinoma endometrioid PIK3CA. high frequency mutations some subtypes gynecological cancers clear cancers) supports proposal new treatment strategy based ATR inhibitor inhibitors.