DNA sequencing has become part of our lives – but what is it? For one thing, it is a big business. In 2003, approximately $3billion US found its way into sequencing enzymes and reagents.
The Journal of the American Medical Association recently carried an article describing the first-generation Human Genome Project called Sanger sequencing that delved into DNA sequencing.
The project lasted thirteen years at a cost of $3 billion US. It was completed in 2003.
About DNA Sequencing
The DNA code is comprised of four chemical bases. They are adenine (A), guanine (G), cytosine (C), and thymine (T). These bases are paired. For instance, A with T and C with G. They form units which are called base pairs.
There are three billion bases in DNA. Almost ninety-nine percent are the same in everyone. The sequence of these bases provides the information needed to build and maintain an organism. This can be compared to letters of the alphabet that are in a certain order and form words and sentences
DNA bases match up with each other, A with T and C with G, to form units called base pairs.
DNA sequencing, a laboratory technique, determines the sequence of bases in a DNA molecule. A DNA base sequence transports information that cells need to build RNA molecules and assemble protein. Thanks to the Human Genome Project, DNA technology is now faster and has become less expensive.
And Now Next-generation Sequencing (NGS)
NGS is also called high-throughput sequencing. NGS represents many different sequencing technologies that have revolutionized molecular biology and the study of genomics.
At one time NGS was considered prohibitively expensive, and its technology was not translatable by most laboratories. Now we have an entirely different scenario whereby NGS is the “go-to” option for mainstream laboratories. Researchers can now generate scientifically accurate data, a major advantage over previously dependable microarrays.
Microarrays determine whether an individual’s DNA contains mutations in certain genes such as BRCA1 or 2. It is not uncommon for companies to produce microarrays using the same techniques as used to produce microchips for computers.
Where NGS Matters Most
Instead of keeping with clinical guidelines, researchers conducting NGS used a universal approach. They found more medically actionable findings than they would have otherwise.
The findings in these genes relate to health conditions that are actionable. Meaning that medically known recommendations exist, and the health care provider is able to act upon them.
The universal multigene panel testing was credited with the detection of actionable variants. This went well beyond what was generally found when the researchers used targeted genetic testing in accordance with current guidelines.
About the Results
The study, involving 2,984 patients with solid tumors, was conducted at three Mayo Clinic cancer centers and a community practice. The patients had received treatment from April 2018 through March 2020. The median age was sixty-one, and over half of the participants were male.
A total of 1,019 patients were reported to have a first-degree family member with a history of cancer. A total of 176 relatives were tested with 79 showing positive results.
One in eight patients were found to have fifty percent more pathogenic germline variants (PGVs) than would have been found following the general guidelines. Germline DNA is tissue that is derived from reproductive cells. It is incorporated into the DNA of each cell in the offspring.
PGVs were discovered in 397 patients. This included 282 moderate and more severe cancer genes. Most common were BRCA1 and BRCA2. Alterations of varying significance were discovered in 1,415 patients.
Eighty-three genes were analyzed. In all, 192 patients showed results that could not have been discovered using family history testing criteria if clinical guidelines were followed.
Additionally, these findings led to treatment changes in about thirty percent of patients tested. The study also identified people who were at high risk prior to the disease developing.
The tests are highly recommended for relatives of cancer patients even if they have not exhibited any symptoms.
However, even when there is no cost associated with testing, very few people have responded, claiming confidentiality and insurance as reasons for not being tested.
Researchers feel confident that this type of testing has the potential to be widely accepted in the practice of oncology.