1708P SMARCA4/SMARCB1 alterations detected through tissue comprehensive genomic profiling (CGP): A single-center study of prevalence and clinical characteristics

SMARCA4 (also known as BRG1) and SMARCB1 are proteins with transcription-regulation through helicase ATPase activity in the SWI/SNF chromatin-remodelling complex. Alterations these genes have been described prognostic related to tumor differentiation metastasis. Inactivation has a role development, early dedifferentiation metastasis of up 20% solid tumors. We performed an observational retrospective study at Hospital Clinico Universitario San Carlos (Madrid) 703 advanced patients undergoing NGS testing their disease between July 2019 December 2021. analyzed clinical data SMARCA4/B1 altered tumors well response systemic treatment, mutational burden (TMB) accompanying genetic alterations. identified 51 (n=41) (n=10) alterations respectively. The most common was NSCLC (n=18, 35.3%), followed by ovarian cancer (n=6, 11.8%), sarcoma 11.8%) or endometrial (n=5, 9.8%). median age 65 years (range 31-89), there similar proportion men (n=23, 45.1%) women (n=28, 54.9%) dominance tobacco exposure (n=31, 60.8%). Median TMB 7.57 mut/Mb 0-189.1), but for 12.61 1.26-60.52). consisted point mutations 34 cases, 4 amplifications, 2 rearrangements single cases frameshift mutation, truncation splicing event. Point were frequent event (n=6). frequently co-altered globally TP53 (n=29, 56.9%), CDKN2A/2B (n=21, 41.1%) ATM (n=12, 23.5%). Immune checkpoint blockade administered 21 9 them got long-term responses. In our cohort, SMARCA4/SMARCB1 presented trend high prolonged responses immunotherapy, especially subgroup NSCLC. information from CGP reports can enrich profiling patients.