Next-generation sequencing, or NGS, has allowed for an unprecedented level of genetic research. Since cancer is one of the biggest killers of human beings, much of this research has been directed toward cures. The new research has led to some significant breakthroughs.
What Makes Next Generation Sequencing Superior to Older Methods?
The speed and scalability of NGS is likely its biggest advantage over older methods such as Sanger sequencing. With the old Sanger system, it took an international consortium over 10 years to release the complete reference human genome back in 2003. Meanwhile, NGS makes it possible to get not just one, but two, sequences from each cancer patient – within a timespan short enough for treatments to be developed for those same patients.
Next generation sequencing started to be developed in earnest right after the 2003 release of the human genome. The amount of time and resources needed to get that first copy showed scientists that they needed to redefine their ideas of what counted as “high throughput sequencing.” Multiple competing technologies went into play, finally resulting in methods that were not only faster, but more accurate than prior technologies. The cost for determining each DNA base pair went down as efficiency improved.
How NGS is Applied to Cancer Research
Next-generation sequencing has been essential for gaining a true understanding of the genetic changes that have taken place within cancerous cells. Its increased speed and lower costs make it feasible to learn the inherited genome of a cancer patient, as well as one of his or her cancer. Then, the genomes are compared to see how the cancer’s genes differ from the original. This allows researchers to precisely pinpoint what has changed.
Other research has focused on specific cancer types across multiple patient samples. The Cancer Genome Atlas, or TCGA, and the International Cancer Genome Consortium, or ICGC, have been on the forefront of such research. The first mainly uses exome sequencing, while the latter focuses on whole genome sequencing. Together, they have studied over 30 types of cancer. These studies have enabled a pan-cancer analysis that has identified recurring mutational patterns across cancer types.
From this information, these consortia has found driver genes implicated in the development of tumors, molecular cancer subtypes, and perhaps most excitingly, a mutational basis for targeted treatment options.
The efforts of these consortia have also made it easier for other researchers to do their work. They have provided tools that allow for the international recording, analysis, and sharing of data.
Focal Points of Current Research
Currently, NGS research is mainly focused on learning how to negate the development of treatment resistance, as well as determining which patients will respond to specific therapies. NGS has allowed the reconstruction of the evolution of driver and other mutations in clonal compartments of cancers, and this provides important information in how cancers evolve to resist treatments. It also is important for figuring out how to reduce treatment resistance.
Next generation sequencing has also made it possible to identify novel transcripts and fusion genes, gain new insights into the tumor microenvironment, and estimate the abundance of different cell types in a mixed cell sample. It has even revealed that non-coding RNAs have at least some involvement in regulating the plasticity of cancer cells, a phenomenon that adds an extra layer of complexity to cancer biology.
These and other discoveries have already occurred due to the use of next-generation sequencing. More are coming quickly as new discoveries and therapies are built on the foundations of this knowledge.