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Track the mutational fingerprints of cancer

2024-05-10 18:00:16

With the ultimate goal of developing better prevention programs, early detection and new treatments against cancer, an international consortium of scientists has promoted the “Mutographs Project”, through which the so-called “mutational fingerprints” present in the DNA of tumor cells.

Researchers from the Ángel H. Roffo Institute of Oncology (University of Buenos Aires), the Italian Hospital of Buenos Aires (HIBA) and its Institute of Translational Medicine and Biomedical Engineering (IMTIB), in Argentina, participate in the ambitious initiative, which recently announced their latest advances in the academic journal Cell Genomics.

“The word ‘Mutographs’ is used to describe the signatures or mutational fingerprints in the tumor’s DNA, which are generated by various factors throughout our lives. These changes escape the cellular repair mechanisms to which our genetic material is subjected and could be involved in the process of cancer development,” Tamara A. Piñero, IMTIB Project Coordinator, executing unit of the project, explained to the CyTA-Leloir Agency. triple dependency between CONICET, the University Institute and the Italian Hospital, and who participates in the international project under the direction of Carlos A. Vaccaro, director of the HIBA Hereditary Cancer Program.

“The initiative – Piñero continued – focuses precisely on identifying and analyzing these traces, given that they can provide valuable information about how environmental factors, our lifestyle or other biological issues generate subtle changes in DNA. By studying them on a large scale and in different populations, we hope to discover and characterize the diverse patterns involved in different types of cancer.”

In the case of HIBA, an interdisciplinary group made up of researchers and surgeons, epidemiologists and anatomopathologists obtained biological samples of colorectal cancer and performed molecular analysis and long-term monitoring of the evolution of the patients recruited for the study.

On the other hand, the Department of Epidemiology and Environmental Carcinogenesis (DEyCA) and the Head and Neck Functional Unit of the Roffo Institute participate in the initiative, contributing their extensive experience, precisely, in head and neck tumors. “This project has managed to create one of the most diverse and complete biorepositories that exist to investigate the causes of eight types of cancer, which have different incidences in the world,” reported Marta Vilensky, head of the DEyCA, and another of the co-authors of the study. .

The biorepository has different types of biological samples, “which include tumor tissues, healthy tissues, blood, plasma, saliva and urine, as well as demographic data and risk factors associated with cancer such as alcohol consumption, tobacco, overweight/ obesity, certain medical conditions and family history,” Vilensky added.

From left to right: Carlos Vaccaro, Alejandra Ferro, Romina Cajal, Tamara Piñero and Juan Pablo Santino, some of the experts from the Italian Hospital working on the project. (Photo: Italian Hospital of Buenos Aires / CyTA-Leloir Agency)

Under the direction of renowned British scientist Michael Stratton, an expert in cancer genetics at the Wellcome Sanger Institute, outside Cambridge, United Kingdom, the “Mutographs Project” brings together specialists from various disciplines and regions of the planet, and is supported by Cancer Research UK, the world’s largest independent cancer research organisation.

So far, the initiative has managed to create a large set of genomic data and a biorepository of almost 8,000 cancer cases from 30 countries on five continents. And completed the genomic sequencing of more than 4,000 cases, with the main objective of understanding the causes of cancer in 8 anatomical sites, about which little is known: esophageal squamous cell carcinoma, renal cell carcinoma, colorectal cancer, pancreatic ductal adenocarcinoma , adenocarcinoma of the esophageal junction, head and neck cancer, urinary bladder cancer and gallbladder cancer.

“This approach allows us to investigate the variations in cancer incidence rates between different regions of the world, comparing the mutational fingerprints in the samples analyzed and crossing this information with the clinical-epidemiological data of the participating regions,” highlighted Piñero. “Mutographs constitutes a legacy for new projects in the field of cancer genomic epidemiology and has the potential benefit of improving oncological management in both the prevention and treatment phases,” he added.

Vilensky, for his part, highlighted that Argentine participation in this project “has allowed us to consolidate the expertise of our institutions in the development and implementation of research protocols in genomic epidemiology in cancer.” And he concluded with a reflection: “Unfortunately, I think it has also highlighted the limitations we face, such as the lack of local and international funding to participate in initiatives of this type, hire and train staff, and be able to follow patients over time.” necessary to document their response to treatment and overall survival.” (Source: CyTA-Leloir Agency)

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