Bladder Cancer Coverage from Every Angle

Potential Genomic Predictors of Outcomes in High-Grade T1 Bladder Cancer

By: Susan Reckling
Posted: Monday, November 9, 2020

To learn more about the molecular characterization of high-grade T1 bladder cancer in an attempt to improve the management of this high-risk subtype of non–muscle-invasive bladder cancer, David J. Kwiatkowski, MD, of Brigham and Women’s Hospital, along with colleagues from Boston and Barcelona performed genetic analyses, focusing on 95 genes known to be mutated in bladder cancer, in an article published in Cancer Research. The investigators believe their results may help determine which patients can safely be treated conservatively and which ones may require surgery.

“While awaiting independent validation, our findings suggest consideration of mutational analysis of high-grade T1 bladder cancers to assess these mutational and copy number features, to improve prediction of good outcome or the risk of recurrence or progression,” the investigators commented.

The researchers performed exome sequencing on 62 high-grade T1 bladder cancers, and 15 matched normal tissue samples. Analyses were focused on somatic mutations, copy number alterations, mutation load, and mutation signatures. Their study centered on 33 patients with good outcomes, 10 patients with recurrence, and 18 patients with disease progression (as well as 1 with an unknown outcome).

They found the mutation burden was highest in those with good outcomes, intermediate in those with progressive disease, and lowest in those with recurrence (P = .017). In addition, “DNA damage response gene mutations were associated with higher tumor mutation burden (P < .0001) and good outcomes (P = .003),” they added. Also associated with good outcomes were ERCC2 and BRCA2 mutations. The mutations most frequently associated with progressive disease were TP53, ATM, ARID1A, AHR, and SMARCB1. Moreover, “focal copy number gain in CCNE1 and CDKN2A deletion were enriched in [those with] disease progression or recurrence,” the investigators noted, and “APOBEC-A and ERCC2-mutant tumors (COSMIC5) were associated with good outcomes.”

Disclosure: For full disclosures of the study authors, visit

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