5 ways whole exome sequencing is changing the way we investigate cancer

5 ways whole exome sequencing (WES) is revolutionizing cancer research

1. 85% of disease-causing variants [1] are found within the exome; therefore, WES may provide researchers with the best cost vs. benefit in terms of the amount of biological insight attributed from a single sample, given WES can be run on mid-throughput sequencers.

2. Current options for tumor profiling include immunohistochemistry (IHC), fluorescence in situ hybridization (ISH) and, more recently, small panel next generation sequencing (NGS). Yet, each of these tests have their limits, including subjectivity and a tendency to miss key variants. WES, meanwhile, can identify single-nucleotide variants, insertions, deletions, copy number changes, and fusions, all of which may drive cancer growth. Among the many things WES can do is capture documented, relevant alterations while at the same time allowing researchers to make new discoveries.

3. Some common concerns around WES are gaps in coverage and the depth of coverage. However, it has been demonstrated that when supplemented with additional hybrid capture probes, it is possible to improve exome panel coverage to catch almost 99% of exons [2].

4. New disease gene discovery is much easier with WES. Every year, an average of 270 new disease [3] genes are discovered, and updating and revalidating panel tests to look for these diseases is expensive and time-consuming. An alternative approach is to have targeted gene sets built out on an exome backbone. This method leverages the advancements that have been made in bioinformatics analysis and allows labs to achieve a more efficient sequencing workflow; this method returns only the relevant genes of the condition the researcher is investigating.

5. Researchers can take advantage of emerging trends in WES by understanding the technical aspects of sequencing. It is much less expensive and more efficient to offer many tests to be performed on the same technical platform. Patient choice and cost will be the driving factors boosting WES past panel testing.

References:  

1. van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C. Ten years of next-generation sequencing technology. Trends Genet. 2014 Sep;30(9):418-26. doi: 10.1016/j.tig.2014.07.001. Epub 2014 Aug 6. PMID: 25108476.

2. Chong, J.X. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. AJHG. 2015;97(2):199-215.

3. Jessica X. Chong, Kati J. Buckingham, The genetic basis of Mendelian phenotypes: discoveries, challenges, and opportunities. Cell Press. 2015 Aug;97(2).