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Detection of mutant KRAS and TP53 DNA in circulating exosomes from healthy individuals and patients with pancreatic cancer
Open accessAbstract
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 KRASG12D and TP53R273H 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 KRASG12D mutation in 39.6% of cases, and TP53R273H mutation in 4.2% of cases. KRASG12D and TP53R273H mutations were also detected in exosomal DNA from IPMN patients (2 out of 7 with KRASG12D, one of which also co-presented with TP53R273H mutation). Circulating exosomal DNA in 5 out of 9 CP patients enabled the detection of KRASG12D mutation. In 114 healthy subject-derived circulating exosomal DNA, 2.6% presented with KRASG12D mutation and none with TP53R273H 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.
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“In pancreatic cancer, liquid biopsy using circulating cfDNA proves valuable for diagnosis and monitoring.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [30]
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“A study successfully detected KRASG12D and TP53R273H mutations in exosomal DNA from PDAC patients, showcasing the potential role of liquid biopsy [30].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [30]
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Metadata
- Authors
- Yang, S., Che, S. P. Y., Kurywchak, P., Tavormina, J. L., Gansmo, L. B., Correa de Sampaio, P., Tachezy, M., Bockhorn, M., Gebauer, F., Haltom, A. R., Melo, S. A., LeBleu, V. S., & Kalluri, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- University Medical Center Hamburg-Eppendorf (DE)
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal (I3S)
- Corresponding author
- Kalluri, Raghu
- ORCID
- Venue
- Cancer Biology & Therapy
- Publisher
- Informa UK Limited
- Published
- 2017-01-25
- Volume
- 18
- Issue
- 3
- Pages
- 158-165
- ISSN
- 1538-4047 (ISSN-L)
- 1555-8576
- PMC
- PMC5389423
- OpenAlex
- W2582660163
- Cited by
- 248
- References
- 42
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 24 · 2023: 27 · 2022: 26 · 2021: 37 · 2020: 38 · 2019: 33 · 2018: 20 · 2017: 13
- FWCI
- 11.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Biology & Therapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Texas MD Anderson Cancer Center ((CA016672))
- National Cancer Institute (P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- circulating exosomes, exosomal DNA, KRAS G12D mutation, pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, chronic pancreatitis, liquid biopsy, early cancer detection, cancer risk assessment, digital PCR
- MeSH terms
- DNA, DNA, Neoplasm, Humans, Mutation, Pancreatic Neoplasms, Case-Control Studies, Polymerase Chain Reaction, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Cell Line, Tumor, Exosomes
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