Cell-free tumour DNA

Cell-free or circulating tumour DNA (ctDNA) is tumour DNA circulating freely in the blood of a cancer patient. Analysis of the fraction of mutant-alleles from ctDNA compared to normal-alleles from the patients normal genome provides opportunities for minimally-invasive cancer diagnosis, prognosis and tumour monitoring.[1]

ctDNA originates from dying tumour cells[2] and can be present in a wide range of cancers but at varying levels and mutant allele fractions.[3] The ctDNA is highly fragmented to around 170 bp and is cleared rapidly after surgery to remove tumours or chemotherapeutic treatment.[1]

ctDNA testing

Protocols to extract ctDNA generally aim to reduce contamination with normal DNA from leukocytes. This is achieved by rapid processing of whole blood by centrifugation to remove all cells, and analysis of the remaining plasma. The utility of circulating tumor DNA in cancer detection and monitoring has recently been shown via targeted sequencing of plasma.

Technologies used for detection of ctDNA[4]
Principle Method Name
PCR based Nested real-time PCR
ARMS / Scorpion PCR
PCR - SSCP
Mutant allele specific PCR
Mass spectrometry
Bi-PAP-A amplification
Digital PCR BEAMing
Droplet-based digital PCR
Microfluidic digital PCR
Targeted Deep Sequencing SafeSeq
TamSeq
Ion-AmpliSeq
CAPP-Seq
OnTarget
Whole genome sequencing Digital karyotyping
PARE

Cell-free DNA was first used medically for Down's syndrome screening using cell-free foetal DNA.

As of March 2016 the US FDA is considering issuing guidance for the licencing of ctDNA tests.[5] At least 5 companies are developing ctDNA tests for cancer diagnosis or screening.[5]

References

  1. 1 2 ctDNA 'Liquid Biopsy' Could Revolutionize Cancer Care. Kelly. Nov 2014
  2. ↑ Circulating tumor DNA: A new generation of cancer biomarkers Burke. Feb 2014
  3. ↑ Real-time liquid biopsies become a reality in cancer treatment. March 2015 doi=10.3978/j.issn.2305-5839.2015.01.16
  4. ↑ Qin, Zhen; Ljubimov, Vladimir A.; Zhou, Cuiqi; Tong, Yunguang; Liang, Jimin (2016-01-01). "Cell-free circulating tumor DNA in cancer". Chinese Journal of Cancer 35: 36. doi:10.1186/s40880-016-0092-4. ISSN 1944-446X. PMC: 4823888. PMID 27056366.
  5. 1 2 Getting Testy Over Liquid Biopsies; CtDNA Tests Attract Interest from Companies, Institutions, and Regulators. March 2016

Further reading


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