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DNA Found in Exosomes in Pancreatic Cancer – with Characteristic Mutations !

We recently commented (here) on the interesting properties of exosomes that were explored as possible messengers within the body including saliva in the context specifically of biomarkers in pancreatic cancer (ductal adenocarcinoma of the pancreas) by Wong and dental colleagues at UCLA.

Exosomes are tiny bubble type structures found in most biological fluids that contain proteins and other substances including messenger-RNA. Apart from other functions, exosomes appear to be involved in cell-to-cell communication within the body.  This makes exosomes a promising target for possible use as diagnostic or screening biomarkers for any number of diseases including pancreatic cancer.

The question of whether exosomes carry full DNA has been unknown, though there have been isolated discoveries of mitochondrial and single strand DNA.

Now comes what seems to be a rather important finding by Kalluri and colleagues from MD Anderson Cancer Center in Houston, together with German colleagues in an article E-published on January 7, 2014 in the Journal of Biological Chemistry, the official publication of The American Society for Biochemistry and Molecular Biology. The researchers studied exosomes that were isolated from two pancreatic cancer cell lines, in addition to exosomes from the serum of patients with pancreatic cancer and those of healthy human controls.

They looked for and were able to find large fragments of double-stranded DNA in these exosomes involved in pancreatic cancer. This appears to be a breakthrough.  Additionally, they found that the entire patient DNA was represented in the pancreatic cancer related exosome samples. And further, critically, that the DNA in the exosomes from the serum of patients with pancreatic cancer showed mutations involving two of the most common mutated genes in pancreatic cancer: K-Ras and p53.

This appears to be a rather startling discovery.  It needs replication and further research; these are early days.  But this line of inquiry may represent a key way station on the route to an effective diagnostic and even screening biomarker for pancreatic cancer.

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Dale O’Brien, MD