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First cancer mutations decades before the disease started


The first signs can be seen years before cancer

By analyzing the entire genome of over 2,600 tumors from 38 different types of cancer, researchers examined the chronology of genomic changes during cancer development. It was found that cancer mutations occurred decades before the diagnosis.

The current study by the Francis Crick Institute and the EMBL’s European Bioinformatics Institute (EMBL-EBI) found that cancer mutations begin decades before the diagnosis. The results of the studies were published in the English-language journal "Nature".

How does cancer develop?

Cancer develops as part of a lifelong process in which our genome changes over time. As we age, our cells can no longer maintain the integrity of the genome after cell division without some errors (mutations). This process can be accelerated by various genetic dispositions and environmental factors, such as smoking. The mutations can cause cells to be incorrectly programmed during life, which can lead to cancer.

Mutation patterns of cancer should be identified

The current investigation was conducted as part of an international collaboration of over 1,300 researchers known as Pan-Cancer Analysis of Whole Genomes (PCAWG). The aim of this project is to identify and catalog the underlying mutation patterns that cause many different types of cancer. Access to this resource has a significant impact on understanding tumor progression and opens up opportunities for early diagnosis and clinical intervention.

Researchers are creating a molecular clock for the human genome

So-called point mutations that occur during normal aging can be recorded to create a molecular clock for the human genome. A scale can be created to estimate the age of some changes in cancer and to measure how far a tumor has progressed.

Where did the evaluated data come from?

Various data from the Pan-Cancer project and The Cancer Genome Atlas (ICGC) were evaluated to create time series for the development of tumors in various types of cancer, including glioblastoma and colorectal and ovarian adenocarcinoma.

Development of tumors can span life

The results suggest that the development of tumors can span an individual's lifetime, so that the mutations that induce cancer progression can occur decades before diagnosis.

Changes noticeable decades ago

It could be observed that changes in the number of chromosomes within the tumor cells typically only appear late during tumor development. However, in some cases, such as glioblastoma multiforme tumors, these changes can occur decades earlier, the researchers report. Usually cells with an odd number of chromosomes do not survive very long, but somehow these cells still survive. They may start a tumor that is discovered many years later.

Results could lead to new diagnostic tests

With more than 30 types of cancer, it is now known which specific genetic changes will occur and when these are likely. Uncovering these patterns means that it should now be possible to develop new diagnostic tests that will detect the signs of cancer much earlier.

Improved understanding of the mechanisms of cancer development?

Understanding the sequence and chronology of the mutations that lead to cancer could help elucidate the mechanisms of cancer development that would otherwise appear unclear due to the many changes in the final cancer cells. The ability to determine whether a mutation typically occurs early or late in the course of cancer can also help in early detection. This would make it possible to define the sets of changes that need to be considered during screening in order to recognize pre-cancer cells in different transformation stages.

Cancer often arises as a result of normal cell aging

The development of cancer is largely an unfortunate consequence of the normal aging of our cells, the researchers report. A complete understanding of the molecular course of the disease is the first step in identifying targets for early detection and perhaps also treatment. Observing that many genetic changes already existed years before the cancer was diagnosed offers the opportunity to detect abnormal cells before they become completely malignant. (as)

Author and source information

This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.

Swell:

  • Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner, Stefan C. Dentro, Santiago Gonzalez et al .: The evolutionary history of 2,658 cancers, in Nature (published February 6, 2020), Nature


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