Unique somatic variants in DNA from urine exosomes of individuals with bladder cancer

Simple item page
dc.citation.firstpage360
dc.citation.journalTitleMolecular Therapy - Methods & Clinical Development
dc.citation.lastpage376
dc.citation.volumeNumber22
dc.contributor.authorZhou, Xunian
dc.contributor.authorKurywchak, Paul
dc.contributor.authorWolf-Dennen, Kerri
dc.contributor.authorChe, Sara P. Y.
dc.contributor.authorSulakhe, Dinanath
dc.contributor.authorD’Souza, Mark
dc.contributor.authorXie, Bingqing
dc.contributor.authorMaltsev, Natalia
dc.contributor.authorGilliam, T. Conrad
dc.contributor.authorWu, Chia-Chin
dc.contributor.authorMcAndrews, Kathleen M.
dc.contributor.authorLeBleu, Valerie S.
dc.contributor.authorMcConkey, David J.
dc.contributor.authorVolpert, Olga V.
dc.contributor.authorPretzsch, Shanna M.
dc.contributor.authorCzerniak, Bogdan A.
dc.contributor.authorDinney, Colin P.
dc.contributor.authorKalluri, Raghu
dc.date.accessioned2022-02-04T19:19:07Z
dc.date.available2022-02-04T19:19:07Z
dc.date.issued2021
dc.description.abstractBladder 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.
dc.identifier.citationZhou, Xunian, Kurywchak, Paul, Wolf-Dennen, Kerri, et al.. "Unique somatic variants in DNA from urine exosomes of individuals with bladder cancer." <i>Molecular Therapy - Methods & Clinical Development,</i> 22, (2021) Elsevier: 360-376. https://doi.org/10.1016/j.omtm.2021.05.010.
dc.identifier.digital1-s2-0-S2329050121000942-main
dc.identifier.doihttps://doi.org/10.1016/j.omtm.2021.05.010
dc.identifier.urihttps://hdl.handle.net/1911/111966
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.titleUnique somatic variants in DNA from urine exosomes of individuals with bladder cancer
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1-s2-0-S2329050121000942-main.pdf
Size:
1.85 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Bioengineering Publications