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

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dc.citation.firstpage360en_US
dc.citation.journalTitleMolecular Therapy - Methods & Clinical Developmenten_US
dc.citation.lastpage376en_US
dc.citation.volumeNumber22en_US
dc.contributor.authorZhou, Xunianen_US
dc.contributor.authorKurywchak, Paulen_US
dc.contributor.authorWolf-Dennen, Kerrien_US
dc.contributor.authorChe, Sara P. Y.en_US
dc.contributor.authorSulakhe, Dinanathen_US
dc.contributor.authorD’Souza, Marken_US
dc.contributor.authorXie, Bingqingen_US
dc.contributor.authorMaltsev, Nataliaen_US
dc.contributor.authorGilliam, T. Conraden_US
dc.contributor.authorWu, Chia-Chinen_US
dc.contributor.authorMcAndrews, Kathleen M.en_US
dc.contributor.authorLeBleu, Valerie S.en_US
dc.contributor.authorMcConkey, David J.en_US
dc.contributor.authorVolpert, Olga V.en_US
dc.contributor.authorPretzsch, Shanna M.en_US
dc.contributor.authorCzerniak, Bogdan A.en_US
dc.contributor.authorDinney, Colin P.en_US
dc.contributor.authorKalluri, Raghuen_US
dc.date.accessioned2022-02-04T19:19:07Zen_US
dc.date.available2022-02-04T19:19:07Zen_US
dc.date.issued2021en_US
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.en_US
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.en_US
dc.identifier.digital1-s2-0-S2329050121000942-mainen_US
dc.identifier.doihttps://doi.org/10.1016/j.omtm.2021.05.010en_US
dc.identifier.urihttps://hdl.handle.net/1911/111966en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.titleUnique somatic variants in DNA from urine exosomes of individuals with bladder canceren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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