Calculate the aggressiveness of cancer
Knowing the chromosomal set of tumor cells, doctors will be able to determine the correct treatment for an oncological patient, American scientists write in the journal PNAS (Stopsack et al., Aneuploidy drives lethal progression in prostate cancer).
Extra chromosomes
As a rule, human cells contain 23 pairs of chromosomes. Any deviation from this number can be fatal for cells. Some genetic disorders, such as Down syndrome, for example, are associated with an abnormal number of chromosomes: instead of 46, there are 47.
Cancer cells also have non-standard sets: some chromosomes may have additional copies, and some may be missing altogether. This condition is known as aneuploidy. In one of the latest prostate cancer studies, scientists from the United States found that higher levels of aneuploidy in tumor cells lead to a much greater risk of mortality among cancer patients.
The results obtained will help to more accurately diagnose the type of cancer. Also, with their help, doctors will be able to determine which patients need more "aggressive" treatment.
"For me, the exciting opportunity here is the ability to get information about treatment, because prostate cancer is a common disease," says Angelika Amon, oncologist at the Institute for Integrative Cancer Research. Koch at the Massachusetts Institute of Technology. She led the study with Lorelei Mucci, associate professor of epidemiology at the Harvard T.H. Chan School of Public Health.
The best forecasts
Aneuploidy occurs when cells make mistakes sorting their chromosomes during division. Most often, this phenomenon in embryonic cells is fatal to the body. The exceptions are when copies of chromosome 21, which causes Down syndrome, chromosomes 13 and 18, which lead to developmental disorders known as Patau and Edwards syndromes, and X and Y sex chromosomes are created. Additional copies of sex chromosomes can cause various disorders, but they usually do not lead to death.
Most cancers also show a very high prevalence of aneuploidy. But here a paradox arises: why does aneuploidy impair the ability of normal cells to survive, while aneuploid tumor cells are able to grow uncontrollably? There is evidence that this phenomenon makes cancer cells more aggressive, but until now it has been difficult to accurately demonstrate this relationship. In most types of cancer, almost all tumors are aneuploid, so it is very difficult to make a comparison.
Prostate cancer is an ideal model for studying the relationship between aneuploidy and cancer aggressiveness, the authors of the study note. Unlike most other tumors, many prostate cancers – 25% – are not aneuploid or have only a few altered chromosomes. This simplifies the task for scientists: they can easily assess the effect of aneuploidy on the progression of cancer.
Scientists from the Harvard T.H. Chan School of Public Health have been studying prostate tumor samples of patients for 30 years. They had information about the genetic sequencing of these samples, as well as data on whether prostate cancer had spread to other organs of patients and whether they had died from the disease.
The researchers came up with a way to calculate the degree of aneuploidy of each sample by comparing the genetic sequences of these samples with aneuploidy data from prostate genomes in the Cancer Genome Atlas. As a result, they found that patients with a higher degree of cancer aneuploidy had a five-fold higher risk of dying from the disease. The same result was obtained after taking into account differences in scores on the Gleason scale, which determines how much prostate tissue is affected.
The results show that measuring aneuploidy can provide additional information to doctors who decide how to treat prostate cancer patients. "Prostate cancer is terribly diagnosed and difficult to treat," says Angelica Amon. According to her, many patients today undergo prostatectomy (surgery to remove part or all of the prostate gland), which can save lives, but at the same time thousands of men die from prostate cancer every year. "Aneuploidy assessment can be an additional way to help inform about the degree of risk and treatment, especially among people who have tumors with high Gleason scores, and therefore they are at higher risk of death from cancer," the scientist adds.
Angelika Amon is now working with researchers from the Harvard T.H. Chan School of Public Health and is finding out whether aneuploidy can be reliably measured from small biopsy samples.
Aneuploidy and aggressiveness of cancer
Researchers have found that chromosomes 7 and 8 are most often copied in prostate tumors. They are currently trying to identify genes located on those chromosomes that can help cancer cells survive and spread. They are also trying to answer the question of why one prostate cancer has a higher level of aneuploidy than another.
In addition, they are also studying other types of cancer, and the first in line is thyroid cancer, which usually has a low level of aneuploidy. Do these tumors have aggressive forms with extra chromosomes? And do they affect the mortality rate from thyroid cancer? – we will be able to find out the answers to these questions only in the future.
"A very small proportion of thyroid tumors are very aggressive and deadly, and I'm starting to wonder if they have aneuploidy," says Angelica Amon.
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