Thirty thousand genes under the magnifying glass of researchers to identify the alterations that can predispose to the onset of neuroblastoma, a childhood cancer whose total incidence in the world is about 15 thousand new cases per year, of which about 140 in Italy. Not only. Precisely the analysis of this large amount of genetic data has revealed how the genetic alterations typical of neuroblastoma are the same that also predispose to other pathologies such as melanoma and congenital heart diseases. This is what is being studied with the Genedren project coordinated by Mario Capasso, associate professor of Medical Genetics at the Federico II University of Naples and head of the bioinformatics service for Ngs Ceinge, the center of the Genedren network active in the field of advanced biotechnologies consisting of a university hospital and Federico II University and which also includes the Neuroblastoma Foundation, an institution connected for purposes and history to the Italian Association for the Fight against Neuroblastoma.
Neuroblastoma
This childhood cancer generally affects preschool children. It is the leading cause of death within the first year of life and the third most common cancer after leukemia and brain tumors. “Currently – he explains Massimo Conte, of the Pediatric Oncology Complex Operating Unit at the Gaslini Institute in Genoa and vice president of the Italian Association for the Fight against Neuroblastoma – overall survival five years after diagnosis is around 70% for all children with neuroblastoma; at the end of the 1980s it did not reach 40%, so we gained about thirty percentage points ”. It is not so good, however, for children with metastatic neuroblastoma at the onset who unfortunately are the majority: “In these cases – continues Conte who is also coordinator of the Italian Group for the Fight against Neuroblastoma for Aieop (Italian Association of Pediatric Hematology Oncology) – the current survival is around 45%, it was 20% in the 1980s. In summary, one in two children with high-risk neuroblastoma can recover today. The result – concludes the pediatrician – is not yet satisfactory, but certainly encouraging “.
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The Genedren project
Progress that has been possible thanks to scientific research also supported by the Italian Association for the Fight against Neuroblastoma as in the case of the Genedren project, a European study that aims to identify the genetic alterations that predispose to neuroblastoma in order to identify the molecules capable of ‘extinguishing ‘the degenerative activity of cancer cells. “The project – explains Capasso – aims to identify the genetic alterations that predispose to the onset of neuroblastoma through an innovative DNA sequencing of all the genes known so far, which number about 30,000”. The mutated genes will be studied to evaluate their potential role as therapeutic targets of molecular drugs. Various Italian centers of excellence join the network of the Genedren project: in addition to the Ceinge in Naples, the Laboratory of the City of Hope in Padua. the Gaslini Institute of Genoa, the Department of Experimental Medicine of Genoa and the Cibio (department of cellular, computational and integrated biology) of the University of Trento.
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The points of contact with other pathologies
As research progresses it is becoming clear that neuroblastoma is characterized by genetic mechanisms common to other diseases. “Neuroblastoma – explains Capasso – is a pediatric tumor that originates from an embryonic developmental defect. In fact, embryonic cells called ‘neural crest cells’, which normally generate different tissues such as those of the heart and adrenal glands, can interrupt their growth phase due to various biological and genetic factors not yet fully known. and therefore generate a tumor “. Hence the conclusions: “This peculiar origin makes the molecular and genetic mechanisms responsible for the development of neuroblastoma common to the onset not only of other tumors, but also of other non-tumor pathologies”. An example of these points of contact between neuroblastoma and other pathologies comes from the group of bioinformaticians and biologists at Ceinge: “Using a huge number of genetic data, my group – continues Capasso – has shown that the genetic variants that predispose to neuroblastoma they are the same ones that predispose to melanoma and congenital heart diseases ”.
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The first results
The Genedren project is still in its initial phase and, although the pandemic has inevitably slowed down research activities, the DNA of about 100 children with neuroblastoma has already been analyzed. “At the same time – continues Capasso – we are investigating some drugs that seem to work against tumors that have the LIN28B gene altered. We hope to be able to achieve the goals we have set for ourselves over the next three years ”. What are the first conclusions that can be drawn? “According to the preliminary data obtained – replies the researcher – we can certainly state that about 10-15% of neuroblastoma cases are due to a genetic predisposition and that there are mutated genes that can be the target of innovative therapies that have the potential to improve the cures of this devastating disease “.
From the desperation of a mother, hope
Waiting with trepidation for the results not only of Genedren but of other researches are of course the patients represented by the Italian Association for the Fight against Neuroblastoma born from the will of mothers and fathers who have experienced the disease of their children, but also on impulse of oncologists frustrated by the scarce therapeutic successes possible thirty years ago in neuroblastoma. “On December 8, 1992, I arrived at the Gaslini Institute in Genoa with my 5-year-old son Luca, who was diagnosed with a high-risk neuroblastoma after 8 days of investigation”, she says. Sara Costa, founding member of the organization she has presided over since 1996. “From that moment, stimulated by the doctors who were treating Luca, with other parents, I founded the Association through which my desperation has been transformed into hope for many. Since then my commitment has been intense and in particular after Luca was overwhelmed by the disease he became a reason for living ”.
The Association’s commitment to research
With the aim of guaranteeing more and more innovative, personalized and effective therapies to all children affected by this tumor, the Association – identified by the image of the funnel – supports various projects. “Scientific research is indispensable and the pandemic amply demonstrates this. Luca, thanks to research, managed to live for 8 years, which was very rare at the time, when there was still no talk of precision and personalized medicine, let alone genomics and immunotherapy “, continues Costa who adds:” In addition to Genedren we finance many initiatives such as, for example, a project for the coordination of clinical and experimental research in Italy, one on immunotherapy with antibodies and a virtual laboratory “. Hence the invitation to join the fundraising for research that sees the 5×1000 among the donation tools available.
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