Patient: 66 years – Male diagnosed with High grade urothelial papillary carcinoma
Clinical Testing:
- Alterations: Y163C, P48S, S9*
- Gene: TP53, CDKN2A, CDH1
Treatment Options: In general CDKN2A deficient tumors can be targeted by CDK4/6 inhibitors such as palbociclib, ribociclib and abemaciclib in different cancers, however, there are studies demonstrating reduced effect/insensitivity towards immune checkpoint inhibitors (ICI) in CDKN2A mutated tumors including urothelial cancers (Adib, Elio et al.2021;Chen, Yiyuan et al.2021). The TP53 mutation also correlates well with poor prognostic outcome and resistance to Chemotherapy undergone earlier.
Indication: This is a case of High grade urothelial papillary carcinoma diagnosed in July 2022. The patient has progressed on the previous line of treatments – Chemotherapy & Immunotherapy.
Research Findings: According to AACR GENIE cases, CDKN2A is altered in 22.29% and TP53 is altered in 45.06% of urothelial carcinoma patients. TP53 Somatic missense mutations are frequent in almost all cancer types (Giacomelli, Andrew O et al.2018) and are also implicated in chemoresistance (Blandino, G, et al.1999 ;Brachova, Pavla, et al.2013 ;Ferraiuolo, Maria, et al.2016). There are studies underway, indicating that abnormal TP53 alterations could be a prognostic marker in the case of urothelial cancers. CDH1 S9* results in a premature truncation of the Cdh1 protein predicted to loss of Cdh1 expression and possible increased cell migration (Al-Ahmadie, Hikmat A et al.2016). There is an ongoing clinical trial (NCT03620643) which studies the efficacy of crizotinib in metastatic CDH1-mutated solid tumor.