Inverted Urothelial Papilloma : Molecular Genetics

Molecular Genetics of Inverted Urothelial Papillomas (IUPs): IUPs have a low mutational burden and show low incidence of LOH for microsatellite markers commonly altered in urothelial cancers. Most IUPs have alterations in MAPK/ERK pathway, predominantly in the form of oncogenic missense mutations in HRAS and KRAS, and occasionally in BRAF. The vast majority of IUPs show no mutations in FGFR3, TERT promoter, TP53, RB1, or chromatin remodeling genes, all of which are known to be commonly involved in urothelial carcinomas. APOBEC mutational signature (apolipoprotein B mRNA editing catalytic polypeptide-like) commonly seen in urothelial carcinomas is also absent in IUPs. Based on their molecular genetic profile (HRAS/KRAS mutant; FGFR3, TERT, TP53, and chromatin remodeling genes wildtype), it appears that IUPs are distinct from low- or high-grade urothelial carcinomas and arise via a different molecular pathway.

References:
1. Isharwal S. et al. Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder. J Pathol. 2019 July; 248(3):260-265. doi:10.1002/path.5261.
2. Akgul M, MacLennan G, and Cheng L. Distinct Mutational Landscape of Inverted Urothelial Papilloma. Invited Commentary. J Pathol 2019; 249: 3-5.