Abstract 780P
Background
Urothelial carcinoma (UCs) is the 10th most common type of cancer worldwide, which is mainly caused by environmental factors and cigarette smoking. However, few reports have shown the genetic factors related to UC pathogenesis. We sought to assess the frequency of pathogenic/likely pathogenic (P/LP) germline mutations in Chinese Urothelial cancer population.
Methods
We retrospectively collected tissue and matched blood samples from UC patients. Genomic profiling of DNA was conducted by next-sequencing technology. 102 genes associated with cancer predisposition were analysed. Only pathogenic/likely pathogenic alterations were included.
Results
Overall, 442 patients with UC were included in this study from Jan 20th, 2017 to Apr 13th, 2020. There were 303 (68.6%) male and 139 (31.4%) female patients. Median age was 66 (range, 19-93). Twenty-eight (6.3%) patients were identified to have germline mutations, including 3 （10.7%） patients with upper urinary tract urothelial tumours. The most frequently mutated genes were BRCA2 (n=7; 25%), PALB2 /TP53/RB1 (n=3; 10.7% each). Most of these patients (n=26; 92.9%) harbored concomitant somatic alterations, and the average mutation number is 5.5 per patient. Twenty-three (82.1%) patients had germline P/LP mutations in DNA-damage repair (DDR) genes, of which 18 (78.3%) had gene inactivation alteration. Besides DDR genes, TP53/RB1/SMARCA4/TSC2 germline variation were identified in 5 patients. Further analysis revealed that patients with P/LP germline mutations were more likely to have early age of onset (age ≤ 45 years) compared with patients with no germline mutations (10.7% vs 4.3%), but there was no statistical difference (χ2=1.153，P=0.283).
Conclusions
This is the first study to explore the spectrum of P/LP germline mutations among Chinese patients with Urothelial malignancies. The presence of DDR germline variants could not only serve as biomarker for immunotherapy in UC, but also provide valuable information for genetic screening.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.