Unique somatic variants in the DNA from urine exosomes of bladder cancer patients

Bladder cancer (BC), a heterogeneous disease characterized by high recurrence rates, is diagnosed and monitored by cystoscopy. Accurate clinical staging based on biopsy remains a challenge, and additional, objective diagnostic tools are urgently needed. Researchers from MD Anderson Cancer Center used exosomal DNA (exoDNA) as an analyte, to examine the cancer-associated mutations and compared diagnostic utility of the exoDNA from urine and serum of BC patients. In contrast to the urine exosomes from healthy individuals, urine exosomes from BC patients contained significant amounts of DNA. Whole exome sequencing of DNA from matched urine and serum exosomes, bladder tumors and normal tissue (peripheral blood mononuclear cells), identified exonic and 3’UTR variants in the genes frequently mutated in BC, detectable in the urine exoDNA and in matched tumor samples. Further analyses identified somatic variants in driver genes, unique to the urine exoDNA, possibly due to the inherent intra-tumoral heterogeneity of BC, which is not fully represented in random small biopsies. Multiple variants were also found in untranslated portions of the genome, such as miRNA-binding regions of KRAS gene. Gene networks analyses revealed exoDNA is associated with cancer, inflammation and immunity in BC exosomes. These findings identify the utility of exoDNA as an objective, non-invasive strategy to identify novel biomarkers and targets for BC.

Zhou X, Kurywchak P, Wolf-Dennen K, Che SPY, Sulakhe D, D’Souza M, Xie B, Maltsev N, Gilliam TC, Wu CC, McAndrews KM, LeBleu VS, McConkey DJ, Volpert OV, Pretzsch SM, Czerniak BA, Dinney CP, Kalluri R. (2021) Unique somatic variants in the DNA from urine exosomes of bladder cancer patients. Molecular Therapy – Methods & Clinical Development [Epub ahead of print]. [abstract]

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