Interestingly, they identified widespread DNA methylation changes that occur at an early stage. The investigators also found a small number of DNA copy number alterations that preceded the development of urothelial carcinoma. In the patient featured in the paper, a founder mutation in the gene ACIN1, which is involved in RNA splicing, was found in the normal mucosa. This mutation continued to expand clonally and was accompanied by the development of other mutations that accumulated during the progression to urothelial carcinoma.
These interesting findings are consistent with the previous studies that show high degrees of sub-clonal heterogeneity in advanced urothelial cancer. A deeper understanding of the field defects that precede the development of urothelial carcinoma is critical for developing strategies for early prevention. As the authors point out, several biomarker panels that include methylation markers are being developed. If these early-stage methylation defects are common in a significant number of urothelial carcinoma patients, this approach could hold promise for the early detection of field changes that pave the way to the development of urothelial carcinoma.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
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