RRC ID 44842
Author Kahlert C, Melo SA, Protopopov A, Tang J, Seth S, Koch M, Zhang J, Weitz J, Chin L, Futreal A, Kalluri R.
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.
Journal J Biol Chem
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.
Volume 289(7)
Pages 3869-75
Published 2014-2-14
DOI 10.1074/jbc.C113.532267
PII C113.532267
PMID 24398677
PMC PMC3924256
MeSH Cell Line, Tumor Chromosomes, Human* / genetics Chromosomes, Human* / metabolism DNA Mutational Analysis DNA, Neoplasm* / blood DNA, Neoplasm* / genetics Exosomes* / genetics Exosomes* / metabolism Female Humans Male Mutation* Pancreatic Neoplasms* / blood Pancreatic Neoplasms* / genetics Pancreatic Neoplasms* / pathology Proto-Oncogene Proteins* / blood Proto-Oncogene Proteins* / genetics Proto-Oncogene Proteins p21(ras) Tumor Suppressor Protein p53* / blood Tumor Suppressor Protein p53* / genetics ras Proteins* / blood ras Proteins* / genetics
IF 4.238
Times Cited 397
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells