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 |
S0021-9258(20)44175-4
|
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 |
T3M-4(RCB1021) |