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The development of this atlas has been possible thanks to the complete genome sequencing of 2023 colon tumors. The data generated from the analysis is accessible to the scientific community
Colorectal cancer is the third most common malignant neoplasm worldwide. Now, a scientific team has achieved a complete genomic map of this cancer, which deepens its understanding and opens the door to improving and fine-tuning treatments.
The description of this atlas has been possible thanks to the sequencing of the complete genome of 2.023 colorectal tumors – the largest cohort. The data generated from the analysis is accessible to the scientific community. The results have been published in the journal Nature.
Spanish participation
The research is led by British scientists and has the participation of female researchers. Claudia Arnedo-Pac y Núria López-Bigas, from the Biomedical Research Institute (IRB) of Barcelona.
«The information obtained will help to better understand how this cancer develops and to better treat patients»
Claudia Arnedo-Pac and Núria López-Bigas.
"This study, as well as many other previous ones, demonstrate the large amount of information that is generated with the sequencing of complete tumor genomes," says Arnedo-Pac, for whom the information obtained will help to better understand how this cancer develops and, as a consequence, to treat patients better.
Colorectal cancer predominates in older people. According to data from the Cancer Observatory of the Spanish Association Against Cancer, it is estimated that 40.203 new cases of colorectal cancer were diagnosed in Spain in 2023, thus becoming the most frequently diagnosed tumor considering both sexes.
«Spain registered 40.203 new cases of colorectal cancer in 2023. It is the most frequently diagnosed tumor in both sexes»
Claudia Arnedo-Pac and Núria López-Bigas.
Although colorectal carcinoma is a common cause of mortality (within cancers), until now there was no such complete description of their genomic characteristics, the authors write in their article.
Sequencing projects for this cancer had been limited to a few hundred cases and/or had been based on sequencing only the exome (part of the genome that codes for proteins, which is about 1%) or a few hundred genes. concrete.
genetic differences
Colorectal cancer can be classified in different ways, one of them based on genetic or molecular differences.
Three main subtypes are distinguished here: cancers with microsatellite stability - short repetitive sequences of DNA - or MSS (for its acronym in English); cancers with microsatellite instability or MSI; and cancers with alterations in proteins that copy or replicate DNA (POLE). Approximately 80% are MSS, 15-20% MSI and 1-2% POLE.
The study in Nature shows, among others, that the MSS group is not a homogeneous entity, which is why the researchers propose classifying it in turn into four subtypes, with different molecular characteristics and differences in disease progression.
250 drive genes
The work, in which one of "the main strengths" is the ability to detect rare characteristics, also identifies more than 250 possible driver genes for colorectal cancer, some of them not previously implicated in this tumor or in other types of cancer.
«In general, cancers occur due to the accumulation of alterations in the genome of a cell and its descendants sporadically during a person's life»
Claudia Arnedo-Pac and Núria López-Bigas.
In most cases, cancers occur due to the accumulation of alterations in the genome of a cell and its descendants sporadically throughout a person's life.
Although all cells naturally accumulate mutations and do not give rise to cancer, sometimes these affect the function of some genes and alter the behavior of the cells; For example, they can cause a cell to divide faster than its neighbors.
Cancers occur when several of these key cellular functions are altered, leading to a uncontrolled cell growth and division inside the body, explains Arnedo-Pac.
Genes that, when altered, promote tumor development are known as driver genes.
To find them, what has been done in this study (and has been done in similar work in recent decades) is to jointly analyze the genome sequences of 2.023 colorectal cancers with computational methods, including some developed in Núria López's group. Bigas.
Alcohol, tobacco and bacteria
Another part of the study, included within the '100.000 Genomes Project' from the United Kingdom, has consisted of identifying mutational signatures, which are combinations of alterations in the genome sequence caused by a specific mechanism, internal or external.
Specifically, the team identified the SBS93 mutational signature, of still unknown origin, as one of the most frequent in this cancer (present in around 33% of cases), specifically in those tumors with microsatellite stability and in those that present at a younger age.
«The SBS93 mutation tends to occur together with other mutational signatures, including some that have been linked to lifestyle factors such as alcohol and tobacco consumption»
Claudia Arnedo-Pac and Núria López-Bigas.
SBS93 has previously been associated with cancers of the esophagus and stomach. "Although we still do not know the mechanism that causes it, we have identified that it tends to occur together with other mutational signatures, including some that have been linked to lifestyle factors such as alcohol and tobacco consumption, suggesting that SBS93 may have a similar origin," continues Arnedo-Pac
Likewise, the team found that between 6 and 13% of colorectal cancers have mutations caused by a strain of E. coli which generates a toxin called colibactin.
Reference: Alex J. Cornish et al. "The genomic landscape of 2,023 colorectal cancers." Nature (2024)
Source: SINC Agency
Rights: Creative Commons.
