Understanding the genetic make-up of cancer could halt its spread

Understanding the genetic make-up of cancer could halt its spread

The cells surrounding a tumor may hold the key to controlling the spread of breast cancer, but imaging these cells in greater detail and better understanding their genetic makeup could make all the difference. Now researchers have found a way to do just that.

The team, led by the Wellcome Trust Sanger Institute (UK) – alongside the European Molecular Biology Laboratory European Institute of Bioinformatics (EMBL-EBI), the German Cancer Research Center and Laboratoire Science for Life (Sweden) – has developed a technique to examine cellular DNA and RNA strands with hundreds of thousands of small fluorescent molecular probes using fluorescence microscopy to scan much larger areas of tissue.

Cellular mutations, influenced in part by activity around cells, often cause breast cancer to grow out of control, says Artem Lomakin, first author of the research, postdoctoral fellow at EMBL-EBI and visiting scientist at the German Cancer Research Center. Breast cancer tumors eventually grow into cell clones and develop different mutations because they are genetically different and have varying responses to treatment.

The new technique also incorporates a genetic mapping of clones based on specific bases. on the site sequencing technology (BaSISS), which helped create quantitative maps of multiple genetic clones in eight tissues of two multifocal breast cancers, covering the main histological stages of early breast cancer progression: ductal carcinoma on the site, invasive cancer and lymph node metastasis (see Fig. 1). Researchers were able to monitor and identify changes in gene expression and their interaction with the surrounding environment (see Fig. 2).

“We want to read cell genotypes, preserving spatial information. For all the cells in a slide, we want to know the genetic background,” says Lomakin. “It’s very complicated because usually there are very few DNA strands, usually two copies per cell. It’s a very, very weak concentration, so it’s particularly difficult.

He notes that there are “a lot of tricks” the team had to do to amplify the detected signals, including developing the probe to target very specific mutations. This involved first determining exactly where in the tumor sample to study – they could then hold and sequence multiple points along the sample.

“That way you’ll get enough resolution because you have bulk sequencing,” says Lomakin. “You will have enough resolution to find out which variants exist and which mutations are attributable to different types of evolutionary lineages.”

The probes designed by his team can be used on alleles, which are slightly different versions of the same genes created by mutations. The new method can provide information about the prominent status of genes in cells. Using a process called rolling circle amplification – where a short DNA or RNA primer is amplified to form a long single-stranded DNA or RNA using a circular DNA template and Special DNA or RNA polymerases – provides researchers with a clearer and more enhanced view of the sample region. It produces “a very, very dense strand of DNA that has a lot of copies,” Lomakin says.

“We can now target specific mutations in specific cells because typically when genes are expressed there are multiple copies per cell,” he says. “When the gene is expressed from DNA, it will also carry the mutation that was in the DNA to the original level.”

The researchers are now continuing the study, further exploring the internal and environmental markers that separate the dangerous evolutionary lines of cancer from those that are more benign. They could also expand cancer research to anything that has an internal cellular structure.

“This technology will allow us to finally have a complete picture of the evolution of cancer,” he says. “Historically, studies were done either en masse or at the level of a single cell. You lose spatial resolution in these cases, so you don’t know which cells are actually cooperating with each other. Technology like ours will be key to understanding how cancer progresses.

The research could also lead to the development of therapies to slow or even prevent cancer cells’ ability to grow and spread by influencing the areas around a tumor.

#Understanding #genetic #makeup #cancer #halt #spread

Leave a Comment

Your email address will not be published. Required fields are marked *