Figure 2
Case examples of UC with significant genomic alterations. (a) FGFR1-NTM fusion in UC. This UC (case 16) presented as a urethral mass in a 73-year-old man who developed metastatic high-grade disease. This tumor was sequenced to a depth of 1037 × , which revealed six alterations including an FGFR1-NTM gene fusion. Additional alterations included amplifications of the CCND3, CDK4, MCL1, MDM2 and MYC genes. (b) ERBB2 (HER2) amplification in UC. This UC (case 17) is a high-grade, advanced-stage tumor from a 57-year-old man. The histology is taken from the transurethral resection specimen used for the NGS assessment. This tumor also featured other potential opportunities for targeted therapies including CDKN2A/B loss, FGFR1, MLL2 and TP53 mutations, and amplifications in CCND1, FGF3, FGF4, FGF19 and RAF1 mutation. (c) PIK3CA amplification and FGFR3 mutation in UC. This case (case 24) is a 58-year-old male patient with a high-grade stage IV UC. NGS was performed on the primary tumor using a transurethral resection FFPE specimen sequenced to a depth of 1059 × . This tumor featured six GAs, one of which was an amplification of the PIK3CA gene. This is the first PIK3CA amplification reported in a case of UC. The tumor also had a R248C mutation in the FGFR3 gene. This tumor’s histology does resemble the large bulky intraluminal growth pattern previously described for FGFR3-mutated UC, but does not clearly show the koilocytotic nuclear changes also attributed to those tumors. This tumor featured additional potential actionable GA in the CDKN2A/B, MDM2 and TSC1 genes as well as GA in KDM6A. (d) ERBB2 (HER2) mutation in UC. This UC (case 10) is a high-grade, advanced-stage tumor from a 71-year-old woman. The histology is taken from the lymph node metastasis specimen used for the NGS assessment. Note that this tumor has a micropapillary architecture. This UC features the S310F base substitution in the ERBB2 (HER2) gene. This tumor also featured mutations in the FBXW7 and TP53 genes.
