Another surprising role for exosomes? Improving next-generation sequencing-based cancer diagnostics in liquid biopsies

Sequencing genetic material from liquid biopsies promises to be one of the most important recent developments in cancer diagnostics. The relative ease and minimally invasive nature of obtaining liquid biopsies makes it an attractive alternative source of tumor DNA relative to direct tumor biopsies. The importance that liquid biopsies constitute a possible source of genetic information about tumors is even further emphasized in clinical situations when obtaining biopsies or surgical material is difficult or practically impossible. However, using soluble, cell-free DNA for diagnostic purposes, despite several remarkable advances in the field, is suffering from several potential drawbacks. The proportion of tumor-derived DNA relative to the total amount of circulating cell-free DNA significantly varies, and it is often too low to allow reliable genome-scale (whole genome or whole exosome) next-generation sequencing-based characterization of the primary tumor. A publication in the current issue of this journal suggests an interesting, exosome-based alternative to obtain tumor-derived DNA or RNA for next-generation sequencing.

Exosomes are small, 30–100 nm cell-derived vesicles that first captured the attention of biologists <30 years ago. Since then, exosome research has matured into one of the most exciting and most surprising research fields in modern biology. Rather than some sort of cellular byproduct, exosomes play an important role in a whole array of biological processes including intercellular communication. Most recently, it was shown that exosome-associated integrins may play a central role in determining the organ target of cancer metastasis. Most importantly for the issue at hand, exosomes contain large fragments (>2.5 kb, perhaps as large as 10 kb) of double-stranded DNA. They also contain a significant amount (read more…)

Genetic alterations detectable in circulating cell-free tumor DNA

exosome rna

Tumor cells release small fragments of cell-free DNA into circulation by multiple mechanisms. Cancer-associated genetic alterations such as point mutations, copy number variations, chromosomal rearrangements, and methylation patterns can be detected in circulating cell-free DNA.

Szallasi Z. (2016) Another surprising role for exosomes? Improving next-generation sequencing-based cancer diagnostics in liquid biopsies. Ann Oncol 27(4):557-8. [abstract]

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