title: Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.
abstract: Exosomes are small vesicles (50-150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.
authors.affiliation: From the Department of Cancer Biology, Metastasis Research Center, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahlert
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Melo
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.forename: Jiabin
authors.initials: J
authors.lastname: Tang
authors.forename: Sahil
authors.initials: S
authors.lastname: Seth
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Juergen
authors.initials: J
authors.lastname: Weitz
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Andrew
authors.initials: A
authors.lastname: Futreal
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D055354:Exosomes / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000235:genetics; D018631:ras Proteins / Q000097:blood / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Chromosomes; DNA; Double-stranded genomic DNA; Exosomes; KRAS; Mutations; Pancreatic Cancer; Serum; p53