2023-05-10 22:42:30
10 mei 2023 – 22:08
Large-scale Dutch DNA data analysis shows important and new insights into differences between primary and metastatic cancer. These insights provide relevant starting points for improving cancer treatment. The results of this research have been published today in renowned trade journals Nature in Nature Genetics. [EC1]
Cancer is caused by DNA changes that cause a cell to gradually change from benign to malignant. This can lead to metastases to other parts of the body. By analyzing the DNA data of more than 7,000 patients, the researchers show that there are major differences between primary and metastatic cancer and that there are also tumor types in which the primary tumor and the metastasis hardly differ from each other! By studying the type of DNA change and the consequences of the changes, important insights into the underlying biological processes have been obtained.
Research with complete DNA information of tumors
Researchers from UMC Utrecht, Hebron Valley in Barcelona and Hartwig Medical Foundation in Amsterdam and Australia have mapped the DNA changes of the 23 most common tumor types. They have studied the differences in genetic characteristics between the source of the cancer, the primary tumor, and metastatic tumors.
Unique collections of whole genome sequencing data from tumors were used. This enabled the researchers to study in great detail which changes in the tumor had occurred during and after the tumor had developed. The researchers have harmonized and systematically compared the world’s largest publicly available data sets of primary tumors (from the international PCAWG consortium with information from ˜2,800 patients) and metastatic tumors (Hartwig Medical Database, ˜4,400 patients).
Difference between primary cancer and metastatic tumors
The main research question was: ‘To what extent are metastatic tumors different from primary cancers?’ The summary answer is: ‘It depends on the type of cancer’. There are tumor types in which there are no significant changes between the primary tumor and the metastasis, such as skin cancer. In other tumor types, such as lung and prostate cancer, many changes are present and the metastatic tumors could actually be seen as completely different tumors than the original diagnosed cancer.
When asked what exactly is different and what processes underlie this, the answer was the same: ‘That also depends on the tumor type’. By looking at the details of the DNA changes, it was often possible to deduce which biological mechanisms were active and at what stage of tumor development these processes took place. In the advanced development of tumors, other processes often appeared to be active than in the development of tumors. Some of the processes found play a universal role in all cancers, but other processes were very specifically present in a few tumor types. Paradoxically, some previously given anti-cancer treatments turned out to lead to many new DNA changes. New features of the cancer could also be found in metastatic tumors that were the result of resistance to previous treatments.
How does a cancer cell escape the immune system?
In the second publication, the researchers took a closer look at the genetic mechanisms that a cancer cell uses to escape the immune system. Due to the DNA changes that have caused the tumor, each tumor cell becomes a little foreign to the body. This is usually a signal for our immune system, also known as the immune system, to recognize and clear tumor cells at an early stage. Thus, a fully developed tumor must have acquired properties to escape this mechanism.
From a genetic perspective, there are several escape routes for this. For the first time, the researchers systematically investigated which pathways are used in different types of cancer and looked at any differences between primary and metastatic tumours. There are roughly six different escape routes that can be distinguished genetically. There are major differences per cancer type in the presence of one of these escape routes, but there appear to be few differences between primary and metastatic tumours. Escaping the immune system is therefore a property acquired early in tumor development. There are also major differences between cancer types with regard to the mechanism used. Some have a diversity of escape mechanisms, while in others only one or a few are found.
Because a well-functioning immune system is essential for the functioning of promising immunotherapy treatment of cancer, the results of this study are relevant for improving therapy choices and preventing overtreatment.
Research leader Prof. Dr. Edwin Cuppen: ‘The new insights from these studies form a valuable basis for improving diagnostics in cancer patients, personalizing therapeutic treatment and possibly preventing (metastatic) cancer. The results of the study make it clear how important the systematic collection and disclosure of data for reuse is in the healthcare domain. Without the cooperation and consent of patients, as well as national-scale collaboration with hospitals, this study would have been impossible. And these new valuable insights for the improvement of future oncological care would not have been possible.’
This research was carried out in the context of the Oncode Institutea collaboration made possible by KWF Cancer Control and ministries of VWS, OCW in NO. Of Hartwig Medical Database is a unique research resource worldwide and was founded by Hartwig Medical Foundationa non-profit organization that partners with the Center for Personalized Cancer Treatment and a large number of Dutch hospitals to improve diagnostics and care of cancer patients.
Over Hartwig Medical Foundation
Hartwig Medical Foundation is a non-profit foundation located in Amsterdam. The foundation aims to improve care for patients with cancer. It does this by advancing cancer research and conducting complete DNA analyzes to give each patient with cancer the treatment that best suits her or him.
Over het Center for Molecular Medicine (CMM)
The Center for Molecular Medicine (CMM) is a research center of UMC Utrecht that focuses on understanding the molecular basis of diseases. More than 180 researchers conduct multidisciplinary fundamental and translational research into various diseases, including cancer and genetic disorders.
About VHIO
Founded in 2006 and integrated into the Vall d’Hebron Campus in Barcelona, the Vall d’Hebron Institute of Oncology (VHIO) is a leading center for personalized medicine in oncology. The goal of VHIO is to conduct research to improve the prevention, early diagnosis and treatment of cancer through a breakthrough model of translational research that consists of converting the latest discoveries in the laboratory into clinical trials at an early stage and consequently in the development of new and more effective treatments that improve the quality of life of cancer patients. VHIO’s activities are made possible by the support of trustees – Generalitat de Catalunya, Fundación Cellex, Fundación ”la Caixa”, Fundación FERO and Fundación BBVA – and the donations of various associations, entities and individuals.
Over Oncode Institute
Oncode Institute unites more than 800 excellent fundamental cancer researchers in the Netherlands. Our mission is to drive innovation in the diagnosis and treatment of cancer. The ultimate goal is to help patients survive, improve the quality of life for those affected and contribute to a more affordable healthcare system. Oncode Institute translates fundamental insights into cancer biology into new diagnostics, new drugs and innovative treatments. The three strategic pillars of Oncode to improve patient outcomes are Excellent Science, Collaboration and Valorisation. Oncode is financed by the Dutch Cancer Society, together with the Ministries of Economic Affairs & Climate, Education, Culture & Science, Public Health, Welfare & Sport, ZonMw and Health~Holland.
[EC1]These links will only become active after the embargo has expired on Wednesday, May 10 at 4 p.m. [EC1]
Bron: Hartwig Medical Foundation
Editorial Medicalfacts/ Janine Budding
I studied physiotherapy and Health Care business administration. I am also a registered independent client support worker and informal care broker. I have a lot of experience in various positions in healthcare, the social domain and the medical, pharmaceutical industry, nationally and internationally. And have broad medical knowledge of most healthcare specialties. And of the care laws from which the care is regulated and financed. Every year I attend most of the leading medical conferences in Europe and America to keep my knowledge up-to-date and to keep up with the latest developments and innovations. Currently I am doing a Masters in Applied Psychology.
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