Genomic Instability Signature of Palindromic Non-Coding Somatic Mutations in Bladder Cancer.

摘要: Numerous pan-genomic studies identified alterations in protein-coding genes and signaling pathways involved bladder carcinogenesis, while non-coding somatic remain weakly explored. The goal of this study was to identify clinical biomarkers regions for cancer patients. We have previously tumors two mutational hotspots occurring at high frequencies (≥30%). These mutations are located close the GPR126 PLEKHS1 genes, guanine or cytosine a TGAACA core motif flanked, on both sides, by stretch palindromic sequences. Here, we hypothesize that such pattern recurrent could be signature genomic instability specifically cancer. analyzed 26 additional mutable sites with same cohort 103 cancers composed 44 NMIBC cases 59 MIBC using high-resolution melting (HRM) Sanger sequencing. Five were additionally gene targeted NGS panel 571 genes. Expression levels three members APOBEC3 family assessed real-time quantitative RT-PCR. Non-coding observed least one locus 62.1% (64/103) tumor samples. co-occurred but absent prostate tumor, HPV-positive Head Neck Squamous Cell Carcinoma, microsatellite (MSI-H) colorectal series. This mutations, specific tumors, not associated patients' outcome more frequent females. Interestingly, burden (TMB) expression APOBEC3B interferon inducible new type targeting loci flanked sequences is promising candidate biomarker early detection relapse major low-cost alternative TMB monitor response immunotherapy