Next-generation Sequencing of Nonmuscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets

This article was published in the Journal of the European Association of Urology in 2017. The researchers wanted to find potential categorical markers that would allow potential diagnosis of nonmuscle invasive bladder cancer (NMBIC). Most sequencing efforts thus far had focused on the muscle invasive bladder cancer (MBIC). Finding such markers would allow clinicians to not only stage but also see the progression of bladder cancer. Tumors were excised from 105 individuals and underwent analysis through next generational sequencing. Variations in the receptor tyrosine kinase/phosphatidylinositol 3-kinase pathway were present in 79% (83/105) of NMIBC tumors. A high prevalence of TERT promoter mutations and chromatin-modifying gene alterations seen in every stage and grade, with a possibility of such alterations to be measurable in urine and be used as a potential screening and/or surveillance biomarker. Another mutation was the ARID1A mutation. This mutation was associated with significantly worse recurrence-free survival after an induction course of BCG. Further work is needed, and this association needs to be confirmed in an independent cohort with ARID1A mutations. Other mutations that the researchers investigated were those in FGFR3 inhibitors, DDR2 and ERCC2 missense mutations. These were systemic check point genes, and they open up the opportunity for the use of systemic checkpoint inhibitor immunotherapies.