Conference Abstracts - 6th Binaytara Precision Oncology Summit: At The Forefront of Targeted Cancer Therapy
Vol. 6, Issue Supplement 2, 2026 · S1-2
Genomic landscape of TP53 Y220C–mutated clinically advanced prostate carcinoma (CAPC)
Varun Nandakumar, MBBS,Philippe E. Spiess, MD,Roger Li, MD,Petros Grivas, MD,Sumanta Kumar Pal, MD,Ashish M. Kamat, MD,Shilpa Gupta, MD,Andrea Necchi, MD,Liang Cheng, MD,Douglas I. Lin, MD, PhD,Ole Gjoerup, PhD,Jerry W. Mitchell, MD,Ryon P. Graf, PhD,Joseph M Jacob, MD,Alina Basnet, MBBS, MD,Gennady Bratslavsky, MD,Jeffrey S. Ross, MD,Neeraj Agarwal, MD
Submission received: 2026-07-11 / Accepted: 2026-07-28 / Published: 2026-09-10
Abstract
Background
The TP53 Y220C base substitution mutation has become a significant therapeutic target with the development of reactivator drugs that restore TP53 function with a regulatory function in the cell cycle. However, its real-world prevalence and associated genomic landscape is not established in CAPC. Data on concurrent genomic alterations (GA) may guide the development of combinatorial therapeutic strategies.
Methods
26,156 cases of CAPC underwent hybrid capture-based comprehensive genomic profiling (CGP) to study all classes of GA including base substitutions, short insertions, deletions, copy number changes, rearrangements and fusions. Microsatellite instability (MSI) status and tumor mutation burden (TMB) were determined from the sequencing data; comparisons utilized the Fisher Exact method.
Results
144 CAPC (0.6%) of CAPC cases featured TP53 Y220C mutation (TP53 Y220C+). Patients with TP53 Y220C+ CAPC had slightly higher mean age (70.0 vs 68.2; p = 0.020). GA potentially associated with CAPC primary hormonal-based therapy response more frequently found in TP53 Y220C+ cases included SPOP (10.5% vs 1.4%; p < 0.0001). GA linked to PARP inhibitor response slightly more frequent in TP53 Y220C+ cases included BRCA2 GA (8.7% vs 3.5%; p = 0.0003) and ATM GA (5.9% vs 4.2%; NS). GA in RAD21 were slightly higher in TP53 Y220C- CAPC (14.8% vs 8.3%; p = 0.029). Additional selected GA, MSI status, and TMB are presented in the table below.
Conclusion
TP53 Y220C is a rare finding in CAPC, but it may offer a potential therapeutic avenue for these patients whose tumors feature such a mutation. In addition, TP53 Y220C+ cases appear to be genomically relatively distinct from TP53 Y220C- CAPC cases and may feature genomic signatures that could influence treatment selection and trial design. Study limitations include a retrospective, descriptive design, a lack of clinical data annotation, and selection and confounding biases, so our findings are hypothesis-generating.