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Unique somatic variants in DNA from urine exosomes of individuals with bladder cancer
- Source :
- Molecular Therapy. Methods & Clinical Development, Molecular Therapy: Methods & Clinical Development, Vol 22, Iss, Pp 360-376 (2021)
- Publication Year :
- 2021
-
Abstract
- 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 needed urgently. We used exosomal DNA (exoDNA) as an analyte to examine cancer-associated mutations and compared the diagnostic utility of exoDNA from urine and serum of individuals with BC. In contrast to urine exosomes from healthy individuals, urine exosomes from individuals with BC 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 frequently mutated genes in BC, detectable in urine exoDNA and matched tumor samples. Further analyses identified somatic variants in driver genes, unique to urine exoDNA, possibly because of 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 microRNA (miRNA)-binding regions of the KRAS gene. Gene network analyses revealed that exoDNA is associated with cancer, inflammation, and immunity in BC exosomes. Our findings show utility of exoDNA as an objective, non-invasive strategy to identify novel biomarkers and targets for BC.<br />Graphical abstract<br />Urine exosome-derived DNA can be used as an objective and novel biomarker for detection of bladder cancer.
- Subjects :
- exosomes
QH426-470
Biology
medicine.disease_cause
microRNA
Biopsy
Genetics
medicine
cancer
Molecular Biology
Gene
Bladder cancer
QH573-671
medicine.diagnostic_test
Cancer
size exclusion chromatography
medicine.disease
Microvesicles
Cancer research
Molecular Medicine
Biomarker (medicine)
bladder cancer
biomarker
Original Article
KRAS
Cytology
extracellular vesicles
Subjects
Details
- ISSN :
- 23290501
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Molecular therapy. Methodsclinical development
- Accession number :
- edsair.doi.dedup.....5bbc9fb99fcfabc6826027f74e306346