Reacción a "Reactions to the finding of new combinations of mutations, 'mutational signatures', associated with specific cancers"

This is a very interesting publication that addressed a pending issue in cancer genomic studies: the optimal identification of mutational signatures in most tumors.

Although these signatures had already been found in the Pan-Cancer project studies, it was known that there were gaps to be filled. In fact, studies published in Nature in 2020 had detected some tumors that, surprisingly, lacked such mutational signatures. This was very rare, since mutational signatures are what ultimately predetermine the mutations involved in the origin and subsequent development of most tumors. In this study the authors developed tools that allowed them to address this problem and solve it successfully.

Another interesting point is that, to increase the sample size and validation of the results obtained, they used genomic data from different sources: one of their own (from UK cancer patients) and two independent ones from international consortia that had been made public. This allowed them to discover several new mutational signatures that had different frequencies in patients and, surprisingly, were generally associated with specific tumor types. This indicates that different tumor types are likely to have different mutational processes.

They were also able to classify the mutational signatures into several categories according to their possible cause: those due to cell-intrinsic processes (arising from failures in DNA replication and repair) and extrinsic ones, due to some carcinogens, metabolic products, environmental factors (some already known such as UV rays or tobacco). Those of the first class could be interesting to develop predictive analyses (their detection would indicate a potential tendency of the individual to develop tumors). Those of the second class would be interesting at a preventive level (avoiding these mutations through changes in diet, exposure to chemical or environmental compounds).

It is important to note that in some cases the researchers were unable to associate the signatures discovered with any known molecular or environmental changes, which indicates that there is still much to be known about how normal cells acquire the mutations that give rise to cancer.

Another important aspect of the work is that they have developed a new computational tool that, from now on, will serve the scientific community to discover such mutational signatures in genomic studies from now on.