Clinical Characteristics and Chemosensitivity in Germline TP53 Pathogenic Variant Cases Identified by Cancer Genomic...

Area of Science:

• Oncology
• Genetics
• Genomics

Background:

• Cancer genomic profiling (CGP) increasingly identifies germline TP53 pathogenic variants (gTP53v).
• Many gTP53v patients do not meet classical Li-Fraumeni syndrome (LFS) criteria.
• Characterizing these cases is crucial for understanding their clinical implications.

Purpose of the Study:

• To characterize clinical features and treatment outcomes of gTP53v patients identified via CGP.
• To compare outcomes between gTP53v and TP53 wild-type (WT) cases.

Main Methods:

• Retrospective analysis of 43 gTP53v patients identified through CGP.
• Analysis of clinical characteristics, molecular features, and treatment outcomes.
• Comparison with 6,515 TP53 WT cases.

Main Results:

• Median age at diagnosis was 38 years; 58.1% had non-core LFS tumors.
• Diverse TP53 variant types were observed with varying allele frequencies.
• Objective response rate to first-line chemotherapy was 62% in gTP53v patients, significantly higher than 32% in TP53 WT cases (p=0.02).

Conclusions:

• gTP53v carriers identified by CGP represent a wider clinical spectrum than classical LFS.
• These patients may have favorable treatment outcomes, particularly with chemotherapy.
• Individualized care is needed, considering atypical presentations, mosaicism, de novo mutations, and clonal hematopoiesis.