Whole-genome sequencing – how it’s done
After an initial investigation, it is decided where the sample for DNA analysis should be taken. In the case of solid tumors, for example a suspected brain tumor, the sample is taken from diseased tissue in the brain. To be able to compare with healthy cells, a blood sample is also needed. In the case of blood diseases such as leukaemia, the sample is taken from the bone marrow where the cancer cells are produced. To obtain a sample of healthy cells, a skin biopsy is performed.
The samples are sent to a pathologist who, through microscopy, determines whether it really is cancer. It is also assessed whether the sample contains enough diseased tissue. This is required for the sequencing to work.
Part of the sample is sent to a genetics department, which produces the DNA sequence. Here, the diseased tumor tissue, or bone marrow sample, is compared against the normal samples to see if there are genetic abnormalities or if they are normal variations.
The response from the geneticists is sent back to the pathologist. A response with information about diagnosis and subgroup is then sent to the treating oncologist. Answers regarding possible hereditary factors may follow later. Remaining tissue is saved in the Children’s Tumor Bank for future research.
Source: Children’s Cancer Foundation
The smoke-like liquid nitrogen curls up from the large cylindrical tanks. Here, neatly organized in rows, tumor samples are stored in small tubes. Brain tumors are found in this particular freezer. The staff who pick up the long boxes where the test tubes are located have both visors and thick gloves, minus 200 degrees requires caution.
The Children’s Tumor Bank at the Karolinska Institutet in Solna has existed since 2010. There are various freezers with samples from several thousand child cancer patients saved here. In addition to tumor samples, there are also blood samples and small, tiny tubes with, among other things, DNA.
“The purpose of the sample collection is to enable research and increase understanding of the children’s disease, improve the diagnosis and, in the long run, adapt and develop the treatment,” says Johanna Sandgren, doctor of medical science and head of unit for the Children’s Tumor Bank at the Karolinska Institutet.
In the Children’s Tumor Bank’s premises, there are large freezers with lots of small tubes with DNA, blood and tissues from children diagnosed with cancer. Affects children’s survival
The Children’s Tumor Bank collects samples from children with so-called solid tumors, basically all forms of cancer except blood cancers. When it became clear in the spring of 2021 that all childhood tumors would be genetically mapped, the Children’s Tumor Bank was an obvious player. The mapping is done as a clinical study in healthcare and samples come from all hospitals in the country that treat and operate on the children.
“It could mean a lot for the individual patient and the chances for a greater percentage than today to survive a cancer disease and have fewer side effects,” says Johanna Sandgren.
Each patient, or guardian, must consent before the samples are saved and analyzed for research purposes. Those who accept also consent to the genetic information being saved and used in the future.
Small sections of tumors are saved in paraffin to be taken out and looked at later.
— We try and must be as clear as we can in our information. It must be clear which analyzes are to be carried out and what the purpose is. But we do not know exactly what type of research methods will be used in the future, so it is important to formulate it reasonably broadly without being too complicated. To withdraw consent at any time and then we remove the samples, says Johanna Sandgren.
Considerations around unexpected findings
It happens that unexpected findings are found when samples are analyzed at the Children’s Tumor Bank, findings that have to do with a disease other than cancer. If the discovery is deemed to be of importance to the patient, the doctor responsible for the patient’s cancer treatment is contacted. Whether and what information is passed on to the patient depends on the situation.
— There are different considerations made by the doctor in charge. Is it a deviation that can be treated? Is it hereditary and should be followed up or can it affect the family? Then we want to be able to inform about those findings, says Johanna Sandgren.
Gabriela Prochazka at the Children’s Tumor Bank studies a digital image of stained tumor tissue. The staining facilitates examination of how the cells in the tumor look and where they are in the tissue.
The analyzes carried out are aimed at the cancer in question. Those that are done within the framework of the healthcare research project are done directly. But other investigations can be carried out much later, when someone has applied and been approved to research the samples, or on the data on genes found in the Children’s Tumor Bank.
This is one of the things that worries Niklas Juth, professor of clinical medical ethics at Uppsala University.
— Since there is so much information that can come out of a test, it is difficult to decide in advance what you say yes to. It could be hundreds of things and there could be new analysis methods that make it possible to find diseases and changes we have no idea about today, he says.
Johanna Sandgren, doctor of medical science and head of unit for the Children’s Tumor Bank at the Karolinska Institutet.
Niklas Juth compares with screening that we have nationally today to detect certain diseases, for example breast cancer and bowel cancer are examples. But before this is introduced, many criteria must be met and approval from the state.
— Whole-genome sequencing is difficult in general and especially for children. It is often the guardians who give consent. But when the child is in his teens, it is the child himself, if he is considered to have sufficient decision-making competence, who must decide. And what happens when the child becomes an adult and perhaps wants something different?
Gene analyzes mean many positive possibilities and Niklas Juth is not against them per se. But at the same time believe that it is good to think through what it is you say yes to because there is a lot of information that comes.
— I think you should think about the points one by one. Am I clear that the main purpose of the genetic analyzes is research or if it is for the treatment of my child? And if there are any unexpected side findings, do I want information about them?