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K. Howarth
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-093 - Assessment of Clinical Applications of Circulating Tumor DNA in Lung Cancer Using an Enhanced TAm-Seq Platform (ID 2270)
09:30 - 09:30 | Author(s): K. Howarth
- Abstract
Background:
Novel biomarkers are required to assess tumor burden and response in lung cancer as conventional biopsies are invasive, costly and only provide a snapshot of the mutational profile at a given time and location. A promising biomarker is the detection of genomic material released from tumors into the blood plasma of patients, known as circulating tumor DNA (ctDNA). ctDNA has been detected in plasma for a wide range of solid tumors and can be distinguished from other (germline) cell-free DNA by the presence of tumor-specific DNA alterations or known hotspot mutations. However, the potential of ctDNA as a biomarker in lung cancer has not yet been fully realized due to technical challenges associated with its detection and analysis, including the short fragment sizes (140-170 bp), small number of amplifiable copies and low/variable allele fractions of ctDNA. To further develop applications of ctDNA in lung cancer, we have developed a process to analyse ctDNA and utilise it in a range of clinical studies.
Methods:
We have developed an enhanced platform for tagged-amplicon deep sequencing (TAm-Seq). Using a combination of improved library preparation and bespoke data analysis methods, this platform can be used to sequence established cancer hotspots and the entire coding regions of selected genes, while preserving high levels of specificity and sensitivity.
Results:
Using this approach, we have developed an assay that analyzes ~20 kb of the genome (including regions of interest in more than 30 genes) with sensitivity down to a few mutant copies. Performance of this assay has been demonstrated using spike-in experiments, dilution series and clinical sample cohorts from lung cancer patients.
Conclusion:
Our proof of concept studies show the potential of ctDNA to be used to assess tumor mutation status, monitor tumor dynamics, assess response to treatment and identify mutations associated with acquired drug resistance and disease progression. This non-invasive approach - a “liquid biopsy” - offers a revolution in how cancer can be detected, monitored and treated. Further studies in lung cancer are being developed and will be presented.
