Detection of mutant KRAS and TP53 DNA in circulating exosomes from healthy individuals and patients with pancreatic cancer

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Yang, SJ (Author) Other; Che, SPY (Author) Other; Kurywchak, P (Author) Other; Tavormina, JL (Author) Other; Gansmo, LB (Author) Other; de Sampaio, PC (Author) Other; Tachezy, M (Author) Other; Bockhorn, M (Author) Other; Gebauer, F (Author) Other; Haltom, AR (Author) Other; Melo, SA (Author) FMUP; LeBleu, VS (Author) Other; Kalluri, R (Author) Other

Journal

Title: CANCER BIOLOGY & THERAPY

Vol. 18

Pages: 158-165

ISSN: 1538-4047

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 134 Citations

Scopus - 134 Citations

Other information

Authenticus ID: P-00M-QS9

DOI: 10.1080/15384047.2017.1281499

Abstract (EN): Pancreatic cancer presents with a dismal mortality rate and is in urgent need of methods for early detection with potential for timely intervention. All living cells, including cancer cells, generate exosomes. We previously discovered double stranded genomic DNA in exosomes derived from the circulation of pancreatic cancer patients, which enabled the detection of prevalent mutations associated with the disease. Here, we report a proof-of-concept study that demonstrates the potential clinical utility of circulating exosomal DNA for identification of KRAS(G12D) and TP53(R273H) mutations in patients with pancreas-associated pathologies, including pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP) and intraductal papillary mucinous neoplasm (IPMN), and in healthy human subjects. In 48 clinically annotated serum samples from PDAC patients, digital PCR analyses of exosomal DNA identified KRAS(G12D) mutation in 39.6% of cases, and TP53(R273H) mutation in 4.2% of cases. KRAS(G12D) and TP53(R273H) mutations were also detected in exosomal DNA from IPMN patients (2 out of 7 with KRAS(G12D), one of which also co-presented with TP53(R273H) mutation). Circulating exosomal DNA in 5 out of 9 CP patients enabled the detection of KRAS(G12D) mutation. In 114 healthy subject-derived circulating exosomal DNA, 2.6% presented with KRAS(G12D) mutation and none with TP53(R273H) mutation. This study highlights the value of circulating exosomal DNA for a rapid, low-cost identification of cancer driving mutations. The identification of mutations in IPMN patients and healthy subjects suggests that liquid biopsies may allow potential assessment of cancer risk but with a cautionary note that detection of clinical cancer cannot be assumed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8