Molecular Characterization of Urothelial Carcinoma of the Bladder and Upper Urinary Tract

Ji Yun Lee; Kyung Kim; Hyun Hwan Sung; Hwang Gyun Jeon; Byong Chang Jeong; Seong Il Seo; Seong Soo Jeon; Hyun Moo Lee; Han-Yong Choi; Ghee-Young Kwon; Kyoung-Mee Kim; Jeeyun Lee; Ho Yeong Lim; Se Hoon Park

doi:10.1016/j.tranon.2017.10.008

Molecular Characterization of Urothelial Carcinoma of the Bladder and Upper Urinary Tract

Transl Oncol. 2018 Feb;11(1):37-42. doi: 10.1016/j.tranon.2017.10.008. Epub 2017 Nov 21.

Authors

Affiliations

¹ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
² Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
³ Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁴ Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁵ Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: hematoma@skku.edu.

Abstract

Purpose: A better understanding of the molecular basis of urothelial carcinoma (UC) is needed to refine the clinical decision-making process.

Methods and materials: We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC) and urinary bladder UC (UBUC) were compared.

Results: Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P=.137). In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%). Frequently detected somatic mutations included TP53 (68.5%), KDR (41.3%), and PIK3CA (17.4%). Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P=.020). The most common types of CNVs included amplifications (56/62, 90.3%): 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4) fusion.

Conclusion: Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.