ABSTRACT
Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.
Subject(s)
Extracellular Vesicles , Genomics , Prostatic Neoplasms , Transcriptome , Male , Humans , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/blood , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Genomics/methods , Animals , Gene Expression Profiling/methods , Neoplasm Metastasis , Mice , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Liquid Biopsy/methods , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Gene Expression Regulation, Neoplastic , Cell Line, TumorABSTRACT
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Subject(s)
Humans , Female , Adult , Masseter Muscle/pathology , Masseter Muscle/surgery , Masseter Muscle , Granular Cell Tumor/complications , Granular Cell Tumor/pathology , Granular Cell Tumor/surgery , Immunohistochemistry/methods , Granular Cell Tumor , Magnetic Resonance Spectroscopy/methods , Biopsy, Fine-Needle/instrumentation , Biopsy, Fine-Needle/methods , Microscopy , Parotid Gland/cytology , Parotid Gland/pathologySubject(s)
Facial Neoplasms/pathology , Granular Cell Tumor/pathology , Masseter Muscle/pathology , Muscle Neoplasms/pathology , Facial Neoplasms/diagnostic imaging , Facial Neoplasms/surgery , Female , Granular Cell Tumor/diagnostic imaging , Granular Cell Tumor/surgery , Humans , Magnetic Resonance Imaging , Masseter Muscle/diagnostic imaging , Masseter Muscle/surgery , Muscle Neoplasms/diagnostic imaging , Muscle Neoplasms/surgery , Young AdultABSTRACT
Aportamos un caso de mesotelioma maligno en unamujer de 37 años con antecedentes de laparoscopia por leiomiomasuterinos. El diagnostico de mesotelioma se estableciópor autopsia. El estudio inmunohistoquímico del tumormesotelial, reveló intensa positividad para CD10, y ausenciade inmunoreactividad para receptores de estrógenos y deprogesterona y calretinina. En nuestra serie de mesoteliomasobservamos que alrededor del 30% de ellos expresabanCD10. En la revisión de la Literatura se observó que aproximadamenteel 40% de los mesoteliomas, mostraban inmunoreactividadpara CD10. En conslusión nuestras observacionesmuestran que CD10 puede expresarse de formaextensa en los mesoteliomas, dato que puede ayudar al establecerun diagnóstico diferencial en estos casos
We report a case of malignant mesothelioma in a 37year-old woman treated for uterine leiomyomas. The diagnosisof mesothelioma was stablished based on autopsystudy. The immunohistochemical study of mesothelialtumor showed strong CD10 immunoreactivity. Our series ofmesotheliomas was also retrospectively studied with anti-CD10 and around 30% of them expressed CD10. Around40% of mestohelioma cases reported in the Literatureexpress CD10. We conclude that CD10 could be expressedin some mesothelial tumors, and may help to stablish a differentialdiagnosis in some cases
