694P Methylthioadenosine phosphorylase (MTAP) deletion is more common in sarcomatoid (srcRCC) than in clear cell renal cell carcinoma (ccRCC)

摘要: BackgroundsrcRCC is an aggressive variant of RCC that frequently presents as advanced-stage disease refractory to traditional systemic treatments for ccRCC. Emerging potential treatment strategies for metastatic srcRCC include immune checkpoint inhibitors (ICPIs) and novel synthetic lethality agents that exploit the genomic loss of MTAP.Methods66 srcRCC and 841 ccRCC underwent hybrid-capture based comprehensive genomic profiling (CGP). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA. Tumor cell PD-L1 expression was determined by IHC (Dako 22C3).ResultsMTAP deletion was significantly enriched in srcRCC compared to ccRCC (15% vs. 6%, P=. 005). CDKN2A/B co-deletion was frequent in MTAP-deleted tumors as a consequence of single 9p21 deletion events. VHL and PBRM1 GAs were significantly increased in MTAP-intact ccRCC, but not in MTAP-intact …