Cell-free DNA represents the key to unlocking tumour heterogeneity (i.e the differentiation of morphological and phenotypic profiles).

Abstract

In recent years, multi-omics data analysis tests have been at the forefront of tumour type identification. Physicians can utilize NGS (next-generation sequencing) to determine the ideal treatment recommendation by taking a more integrative approach to the molecular characteristics.

Tissue vs Liquid Biopsy

Unlike single cancer tests (i.e. tissue biopsy), multi-cancer earlier detection (MCED) tests can detect cancer from a single blood draw. The process for a tissue biopsy occurs after the patient's tumour site is predicted and determined (see Our Plan  for more context towards cancer stage classification in diagnostics) which provides time for the tumour to metastasize further and spread beyond the origin of the primary area for diagnosis. By implementing liquid biopsy tests via NGS (next-generation sequencing), patients are less likely to endure the risk of disease progression through this screening-based technique.

Screenshot 2023-05-09 at 11.32.57 AM.png

Liquid Biopsy Cancer Biomarkers

Cell-free DNA (cfDNA) emits into the person’s bloodstream during a tumour or other microorganism in the body. The liquid biopsy protocol can allow us to assess cancer through a blood draw. Tumours also release signals from dead tumour cells, known as circulating tumour DNA (ctDNA). An NGS assay must sequence whole exome data extensively. [(’exome represents less than 2% of the genome - Illumina/Cancer Exome Sequencing)](https://www.illumina.com/areas-of-interest/cancer/research/sequencing-methods/cancer-exome-seq.html#:~:text=Sequencing the cancer exome provides,alternative to whole-genome sequencing.). Once extracted, the liquid biopsy must undergo a DNA extraction method for ctDNA data optimization. While the ctDNA data only reflects from the direct tissue source removed, NGS is used to ensure DNA fragmentation and sequencing.

Screenshot 2023-05-09 at 1.20.17 PM.png

Methylation Patterns

While methylation patterns are unique to every cell type, the differences within ctDNA methylation patterns provide data towards regions of increased tumour suppressor genes (this is often characterized as an early detection biomarker for lung cancer).

Sequencing alone is not enough.

Just sequencing ctDNA mutations alone does not provide an adequate foundation to detect early-onset cancers. Despite these efforts, ctDNA methods tend to pick up on modifications once they reach 1-2cm in size. By incorporating multi-omics testing, we can ensure more accurate testing solutions.

Source - Ark Investment Management LLC, 2023 (Big Ideas 2023, pp 91)

Source - Ark Investment Management LLC, 2023 (Big Ideas 2023, pp 91)

Lung Cancer is the MOST lethal cancer worldwide. (Source)

The best way to reduce lung cancer deaths would be through primary prevention via NGS liquid biopsy analysis. To ensure the viability of cancer screening, combining low-dose CT scanning can directly increase diagnosis detection.

Source - Ark Investment Management LLC, 2023 (Big Ideas 2023, pp 91)

Source - Ark Investment Management LLC, 2023 (Big Ideas 2023, pp 91)