Introduction

Our previous work has demonstrated that 30 genes are publically mutated in a cohort of patients with recurrence of non-muscle invasive urothelial carcinoma tumors of the bladder (NMIBC). The most common of these were MLL2 (54%) and MUC16 (38%), which have demonstrated a role during tumoriogenesis. Herein we examine both to identify mutational hotspots for NMIUC of the bladder.

Methods

30 tumors from 13 patients with recurrent NMI UC bladder were examined from an IRB approved database. The median follow-up was 26 months (range=6-180). Whole-exome sequencing (WES) was used to identify mutated genes. Public mutation was defined as that seen in 2 or more tumors in a given patient. Tumors were then compared to samples from the TCGA cohort, both in UC where the majority of samples are in muscle-invasive disease, as well as to other cancers.

Results

No mutation hotspot was found for MLL2 but one for MUC16 in the coding region for tandem SEA domains was seen (p<0.0001) (Figure 1). No MUC16 hotspot was found in lung, colorectal or kidney cancer samples from TCGA; neither was it found in the cohort&[prime]s UC samples. No MLL2 hotspot was found in any cancer from the TCGA samples. Analysis of other identified genes within the mucin family did not show mutational hotspots (see Figure 2).

Conclusions

MUC16 of the mucin family of genes represents a unique mutational hotspot in recurrent, NMIBC of the bladder that is not seen in muscle invasive disease. In addition, several studies have demonstrated that MUC16-as part of focal adhesion signaling could play a critical role in facilitating tumor growth and metastasis. Our finding indicates MUC16 may potentially drive NMIBC and its recurrence and represent a potential therapeutic target for recurrence of NMIBC.

Funding

none