The following is the transcription of the above YouTube video, explaining how DNA sequencing of tumor cells can guide treatment. Thanks to the University of North Carolina for posting this. A terrific explanation. (And it’s OK to view it a few times!)
“You were composed of cells–lots and lots of cells. Each of your cells contains DNA which is its instruction manual. If you are exposed to lots of things that cause cancer, so are your cells. If you lay in the sun, your skin cells get burned. If you smoke cigarettes, your lung cells get their nicotine fix. Exposure of cells to carcinogens can damage their DNA. Sometimes when cells divide, DNA can be damaged–just by bad luck.
Damage to DNA is usually repaired, but sometimes it is not. When damaged DNA goes unrepaired, the cells receive bad instruction, and can turn from a healthy cell to a cancer cell. Cancer cells divide too fast and crowd out other cells and grow with they are not supposed to grow. When cancer cells cling together, they form a tumor that might be found by a doctor or a patient.
Today most patients are treated based on what a piece of tumor looks like when viewed under the microscope. This is how oncologists have done it for 50 years. While this approach is better than nothing, it doesn’t work that well. Even if doctors agree what type of cancer a patient has, it does not always mean it is clear what is the best therapy to treat that patient’s cancer.
Recently, it has become clear that the cells instruction manual the DNA determines how s the cancer will to behave and in particular, it determines if it will grow quickly or slowly, if it will respond to one kind of therapy or another, and if it will be cured or come back.
Given that the cancer’s DNA is so important in determining how it will behave, doctors and scientists at the UNC Lineberger Comprehensive Cancer Center have determined to treat patients based on their and their tumor’s DNA. This approach relies upon new DNA sequencing technology, called massively parallel sequencing or next generation sequencing. So we call the Lineberger effort “UNseq”.
Here’s how it works. When a patient with cancer comes to UNC and agrees to participate in our study. Some normal DNA is taken from the patient, usually their blood and some DNA is collected from the tumor. From the tumor DNA and normal DNA are broken into smaller pieces and the importance pieces of the DNA are captured. This capturing is important so we don’t have to sequence all the DNA of a patient, just the DNA which is important in cancer. It is like going into a gigantic library and choosing the one book on cancer ignoring all the other books on eye color or heart size or height.
The captured DNA from the tumor and the normal tissue are then processed using next generation sequencing. After sequencing, we have two gigantic books of DNA sequence. One is the tumor’s DNA and the other is the patient’s normal DNA. Although the captured DNA is much smaller than the patient’s entire genetic sequence, each book is still several million letters long.
The tumor DNA book and the normal DNA book are then compared letter by letter. In most places the books are the same, but in a few places the letters are different. These differences represent mutations in the DNA, that resulted from DNA damage. Finding all the mutations involves a lot of math, but eventually, UNseq identifies all the mutations that are present in the cancer cell and not in the normal DNA .
Just having a list of the mutations is not the end, however. Only a small number of the mutations change what the cancer cells do. Most mutations are harmless. Whether a mutation is good or bad, largely depends on what gene it affects and what part of the gene it affects.
Once the list of mutations has been identified, a team of doctors sits down together and review the mutations at the molecular pathology tumor board or the MTB. Each mutation is reviewed. Some mutations are clearly innocent. Some mutations are clearly bad. For some mutations, it is unclear of their importance and the MPB not always certain what to do with these.
This is all done by doctors were not directly involved in the patient’s care, s so that similar decisions are made about the same cancer.
Once the bad mutations are found, they are confirmed by another clinically approved test. Information about the mutations that are confirmed is given to the patient and their treating doctors.
With this knowledge, the patient’s care can be more tailored or focused. The doctor may decide the patient to try a different therapy. The doctor may decide that the patient has a better or worse chance of recovery. Sometimes the DNA looks makes the cancer look like a different cancer than was found under the microscope. New treatment plans based on DNA sequencing are called targeted therapy.
Importantly, UNseq does not put patients at risk. If there is a good therapy for their cancer, they get that therapy. UNseq only changes care for patients who do not have any good options left. Unfortunately, that is a common problem for cancer patients.
Some day soon, we believe all cancer treatment will be targeted, that is based on what the tumor DNA, rather than what the tumor looks like under the microscope.
Doctors at UNC recognize that technology moves at a rapid pace, but applying new technology to patients can be slow for patients with advanced cancer. Having successfully implemented UNseq, UNC physicians are building upon the approach to develop a range of advanced tests for patient care. We believe that these new approaches will help patients with cancer live longer and better lives.”