Abstract 206P
Background
The key roles of the TP53 mutation in cancer have been well established. However, the different biological processes of urothelial carcinoma (UC) stratified by the TP53 mutation status has not yet been described. Mutational signatures can reveal biological processes underlying carcinogenesis.
Methods
Patients diagnosed with UC were enrolled in the study. Tumor tissue and matching blood were sequenced by next-generation sequencing (NGS) techniques with Acornmed panel with 808 cancer-related genes.
Results
A total of 139 patients were enrolled including 69 patients with TP53 mutation and 70 patients with TP53 wildtype. In TP53 mutation cohorts, the five most frequently mutated genes were TP53 (100%), KMT2D (55%), RB1 (29%), KMT2C (26%), and FAT1 (25%). For TP53 wildtype cohorts, the five most frequently mutated genes were KMT2D (43%), FGFR3 (30%), FAT1 (28%), BRD4 (26%), and KMT2C (25%). For top 20 gene, 4 frequently mutated genes were significant difference between TP53 mutation and TP53 wildtype cohorts, such as ERBB3, FGFR3, ERCC2, and STAG2, excluding the TP53 gene. C to T (C>T) substitutions and transitions were dominant mutation types in both cohorts (39.8% and 44.0%, 50% and 55%, respectively). APOBEC Cytidine Deaminase (Signature 2) were shown in both cohorts. Surprising, exposure to aristolochic acid (Signature 22) and defective DNA mismatch repair (Signature 6) were only existed in TP53 mutation cohorts, whereas spontaneous deamination of 5−methylcytosine (Signature 1) and defects in polymerase POLE (Signature 10) were only discovered in TP53 wildtype cohorts.
Conclusions
There were characterized the genomic differences and similarities, stratified by the TP53 status, which may reflect the UC patients with TP53 mutation harbored a specific biological process.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H.H. Liu, X.Y. Liang, L.B. Chen, Y. Zhang, H.N. Wang, F. Lou, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd.
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