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Investigation of the continuing evolution of cancer

Investigation of the continuing evolution of cancer

A team of researchers led by the Helmholtz Association Max Delbrück Center for Molecular Medicine (MDC), Francis Crick Institute, and University College London reported gaining or missing in certain cells. Large chromosomal fragments, but not in other cells. This is a process that demonstrates the continuous development and selection of preferred features. Findings in the journal Nature are common in 22 tumour types, including breast cancer, colorectal cancer, and lung cancer. President of MDC Evolution and Cancer Genomics Group and one of the paper's senior authors, Dr Roland Schwarz said: "The proposition in this cancer genome is much faster than we expected at the rate of evolution. It is also higher than the usual predictions.

This mutation appears to be more prone to replicating the largeosomal segment containing genes beneficial to cancer cells and losing gene segments that have effective tumour-suppressing effects. "This is logical, but it has never been proven to occur consistently in many tumour types," Schwarz said.

Mother or Father First?

Schwarz and first article writer Tom Watkins, a PhD. The student at the Francis Crick Institute supervised by Schwarz has worked over the past five years to develop a method that helps clarify these major ongoing mutations in much more detail. These are the opposite chromosomes, write all the chromosomes that are much larger than the exact uniform "point" mutations. Specifically, they wanted to know if there was a change in the maternal copy of a chromosome or the paternal copy or both, and the messages came from.

“Ongoing chromosomal instability and the resulting copy number heterogeneity within it may inform treatment approaches,” says Watkins.

Using an algorithm called "refphase" and flexible analysis, they were able to obtain these fine haplotype details. Together with their colleagues, they applied the approach 1,421 samples from 394 tumours representing 22 tumour types. Critically, these samples were all taken from at least two different parts, which allowed the researchers to distinguish between features.

"These datasets are quite rare, so I was excited to study the largest multi-region pan-collection," says Marina Petkovic, PhD doctor. He is a PhD student at Schwarz's lab, part of the MDC's Berlin Institute for Medical Systems Biology (BIMSB), and a second author on the paper.

When they studied different parts of the tumours, they found great variation in gains and losses among them. This high level of variability was found in all tumour types analyzed.

Common Imbalances

The team often found that in one part of the tumour, a gain or loss was only in the maternal copy of the chromosome, but the other user was only in the paternal copy of the gain or loss. This phenomenon, which Schwarz and colleagues first named in a market they did in 2017, is called "mirrored subclonal allele imbalance" (MSAI). "These MSAI events are present in many tumour types, we find them everywhere," says Schwarz.

These imbalances may point to separate evolutionary events in parallel, and this is also thought-provoking. More research needs to be done to better understand whether chromosome segments gained or lost are truly beneficial or random. But one thing is certain, this bulgur provides strong evidence that it is constantly reshaping the cancer genome, also called a chromosomal imbalance.

It addresses an ongoing debate in the field of cancer genomics. Some claim in a series of reports at the beginning of a tumour's life, but in this case, the genome remains comparative. Others, including Schwarz and colleagues, suspect these changes persist throughout cancer's life. "Our approach provides evidence of ongoing chromosomal instability to display an image that was previously impossible," says Schwarz.

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