Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer

被引：794

作者：

Kahlert, Christoph ^{[1
,2
]}

Melo, Sonia A. ^{[1
]}

Protopopov, Alexei ^{[3
]}

Tang, Jiabin ^{[3
]}

Seth, Sahil ^{[3
]}

Koch, Moritz ^{[4
]}

Zhang, Jianhua ^{[3
]}

Weitz, Juergen ^{[4
]}

Chin, Lynda ^{[2
,5
]}

Futreal, Andrew ^{[5
]}

Kalluri, Raghu ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Metastasis Res Ctr, Houston, TX 77030 USA

[2] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, D-69120 Heidelberg, Germany

[3] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA

[4] Tech Univ Dresden, Dept Gen Visceral & Thorac Surg, D-01307 Dresden, Germany

[5] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2014年 / 289卷 / 07期

关键词：

Chromosomes; DNA; Exosomes; p53; Pancreatic Cancer; Serum; KRAS; Double-stranded genomic DNA; Mutations; TUMOR; MICROVESICLES; CELLS; VESICLES; MICROENVIRONMENT; FORM;

D O I：

10.1074/jbc.C113.532267

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3869 / 3875

页数：7

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