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Genomics

Unfolding the Code of Cancers Using the Next Generation Sequencing

Christie Siu—McMaster University Honours Life Sciences 2023

By accessing multiple genes in a single assay to identify causative  mutation, next-generation sequencing provides a more efficient and  deeper look into molecular underpinnings of patients’ tumors. 

Not so long ago, it seemed mapping and understanding the entire human genome  sequence was one of the most expensive and time-consuming studies to accomplish. The  Human Genome Project, initiated in 1990, took a total of 13 years and about $3 billion  USD to determine and study the complete human genome, by using the traditional DNA  sequencing technique—”Sanger sequencing.” Yet, the advent of next-generation  sequencing (NGS) has made a great impact on clinical and molecular biological  research, more specifically—cancer research, leading to the molecular age of cancer. 

Before the 1990s, DNA sequencing was accomplished in an “old fashioned” way by adding agarose gel  and targeted genomic bases manually. Later, the Sanger sequencing technique was introduced into the  biological market and allowed researchers to process long DNA fragments at one time. And the  researching technique evolved, Next-generation sequencing has altered the way that sequencing was  ever performed. Although the invention of the Sanger sequencing did allow researchers to map out the  entire human genome sequence, it is unexpectedly costly and time-consuming for diseases diagnosis  and implantation of treatments of patients, especially individuals that are aware or not aware that, they  themselves are suffering from cancers (1). 

Cancer is one of the most leading cause of death worldwide. According to the National Cancer Institute,  there are related deaths in 2018. In addition the the enormous number of cases that can be studies,  cancers are generically complex and requires high-accuracy targeting specific variants and activation  pathways. Undoubtedly, the success of the Human Genome Project, along with the increased  affordability of sequencing, has implanted the wide use of genomic data to assist in cancer diagnosis and  medicine precision. The development of Next-generation sequencing, once thought to be a novelty,  allows researchers to capture and process a massive amount of genomic information about a cancer in  the shortest time one can imagine- taking only about 4 hours to complete a run (2).

Global Cancer | HEAT: Health Evaluations + applied Therapeutics
SOURCE: GLOBOCAN 2018
Individuals in both the developed and developing countries experience cancers, while most patients  were concentrated in Europe and Asia (3). 

Next-generation Sequencing VS Sanger Sequencing  

In principle, the concepts behind the two DNA sequencing techniques are similar. Both of NGS and  Sanger sequencing requires addition of DNA polymerase to the fluorescent nucleotide according to a  growing DNA template strand, while each nucleotide is identified by their fluorescent tag. But in NGS,  DNA fragments are massively parallel, which allows tones of fragments to be sequencing in just a single  trial. Whereas sanger sequencing sanger sequencing only produces one forward and reverse read of a  single fragment, and in other words, researchers have to be determinant when deciding which DNA  fragment, they are interested in.

When Do I Use Sanger Sequencing vs NGS? - Behind the Bench
SOURCE: Natalie Gurson, ThermoFisher Scientific
The fundamental approach of identifying target DNA sequence in NGS and Sanger sequencing is  similar, but their sequencing volume are different. While only a single DNA fragment can be  sequenced at a time in Sanger sequencing, and alternatively, NGS is massively parallel, millions of  fragments can be translated into genes simultaneously in a single run. 

Compared to the traditional way of sequencing, NGS offers high accuracy, sensitivity, and speed in  genomic investigation (4), as it only requires as little as 5% of the DNA sequences from a tumor sample,  and it can reduce the need to preform multiple tests to examine causative mutation within a patient.

References

1. Vincenza Precone, Valentina Del Monaco, Maria Valeria Esposito, Fatima Domenica Elisa De Palma,  Anna Ruocco, Francesco Salvatore, Valeria D’Argenio. Cracking the Code of Human Diseases Using Next Generation Sequencing: Applications, Challenges, and Perspectives. *BioMed Research International*,  vol. 2015, Article ID 161648, 15 pages, 2015. Available from: https://www.hindawi.com/journals/bmri/2015/161648/.

2. Gurson N. When Do I Use Sanger Sequencing vs NGS? – Behind the Bench [Internet]. Behind the  Bench. 2021 [cited 11 March 2021]. Available from: https://www.thermofisher.com/blog/behindthebench/when-do-i-use-sanger-sequencing-vs-ngs-seq-it out-7/.

3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018:  GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J  Clin. 2018;68(6):394–424. 

4. NGS vs. Sanger sequencing. (n.d.). Retrieved March 11, 2021, from https://www.illumina.com/science/technology/next-generation-sequencing/ngs-vs-sanger sequencing.html.

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