Chilean scientist makes key discovery about mesothelioma, a strange and unknown cancer

Cancer has been cataloged by the World Health Organization as one of leading causes of death worldwide so much so that the year 2020 caused the death of almost 10 million people. Experts predict that by 2040, 16.5 million human lives could be lost to this disease, in which abnormal cells in the body multiply uncontrollably, destroying normal tissue and tumor cells do not die like they should. In Chile, cancer is currently the first cause of death in the population.

Faced with this reality, the first international scientific journal Natural geneticsaudience an article on the molecular study of the malignant tumor of pleural mesothelioma (MPM), caused by exposure to asbestos entitled “Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles underlying intertumoral heterogeneity » about the research carried out in France by Dr. Alex Di Genova, an academic at the Institute of Engineering Sciences (ICI) of O’Higgins University (UOH), while doing his second post-doctorate in the Rare Cancer Genomes team at the International Agency for Research on Cancer (IARC).

Di Genova was part of the research led by IARC’s Rare Cancer Genomics Group, led by Dr Lynnette Fernandez-Cuesta and Dr Matthieu Foll. based on 120 samples from patients with this disease, sequencing for the first time of the complete genome of these tumours.

“We carry out a study of 120 tumors produced by exposure to asbestos, with the aim of understanding the interaction between functional biology and its genomic history. Traditionally, these cancer studies involve genomic sequencing of healthy and tumor tissues, which are then compared to determine mutations. To solve this problem, I developed an algorithm based on machine learning which allowed us to discover with very high precision all the mutations that were in these tumors”, explains the academic.

Since this research involved the first complete study of the genome of these patients, Dr. Di Genova points out that, from a scientific point of view, it was known that the driver genes of this cancer, such as BAP1, NF2 and RBFOX1, they were mutated in 25% of cases, but when they integrated the new information, the new types of mutations and the whole genome, they observed that this frequency could increase by up to 70%. “There were 30% of cases that were lost without making a complete genome, because we did not know what the pilot mutation of this tumor was”, he specifies.

In addition to the above, the UOH academic points out that another of the great advantages of whole genome sequencing for analysis was to be able to describe for the first time mutational processes whose existence was unknown in this type of tumor. For example, in 25% of tumors we detected a process called “chromotripsis”, which is a crisis at the level of one or two chromosomes, where that chromosome is rearranged, generating an advantage and allowing more accelerated cell development. It is a process of punctual evolution which had not been described before”, specifies the scientist.

The research is also notable for determining the wide variability in genomic history, cancer progression, and gene mutation over the years in the 120 patients. Concerning this situation, the academic comments that he realized that “all the patients had a different genomic history, which implied that if I had only one treatment for the 120 patients, it is clear that they would not not all respond in the same way. This tumor is very aggressive and nearly 90% of patients die within the first year of detection and only 5% reach 5 years, and part of it is due to the fact that conventional medicine does not take this genomic variable into account in the treatment stages”.

On how they resolved this variability, he clarifies that they had to construct molecular maps, integrating all the molecular and clinical information of the patients, before which they detected that all the tumors were a combination of three specific profiles: For example, there was a profile that interacted with the immune system and these patients could potentially benefit from immunotherapy. In summary, the greatest implication of this work has been to uncover a large variability, and to detail what are the extreme profiles of this tumor, which would allow progress in more personalized treatments for each patient”, explains Di Genova.

O’Higgins University, in collaboration with the Regional Hospital of Rancagua (HRR), seeks to replicate the study conducted in France by the IARC, by training a multidisciplinary team of researchers, led by Di Genova, to carry out molecular characterization of breast and gallbladder cancer.

“At UOH, we already have the capability to sequence and analyze complete cancer genomes. Currently, with the HRR, we are carrying out a pilot study on breast cancer, which is one of the most frequent in our Region, to search for the genes which contribute to the early onset of this cancer in women. We have a cohort of 100 patients who developed the tumor before the age of 40. And if we can determine which gene or genes are mutating with this molecular study, specialists could apply preventive procedures for these cases and improve their life expectancy, ”underlines the academic of the UOH.

He also adds that he hopes to conduct this research also with gallbladder cancer, which is common in Chile but rare worldwide.