Two rare inheritable variants of a specific gene could predispose to the development of acute lymphoblastic leukemia and myelodysplastic syndrome. The study adds a new piece of knowledge about the history of these diseases, but confirmation is needed
Why do children get cancer? If for at least a third of cases in adults we know the role that improper lifestyles can play (such as smoking, obesity and overweight, unhealthy diet, sedentary lifestyle, alcohol abuse), to which environmental and hereditary factors are added (responsible in any case of a much smaller proportion of neoplasms), much remains to be understood for the risk factors in children. one of the many questions that scientists around the world have focused on for years and now a group of researchers from the Tettamanti Foundation of Monza they first identified two rare germline (transmissible) variants of a specific gene, called SEASON1which could be linked in a small percentage of cases to the development of some blood cancers in pediatric age.
Causes of Cancer in Babies
Every year around the world over 300,000 children and adolescents are diagnosed with cancerThere are about 60 different subtypes of tumors that affect the youngest and in Italy there are more or less 1,500 diagnoses per year in the 0-14 age group and 900 in the adolescent age group, between 15 and 19 years. Although healings are on the rise (today over 80% of very young patients recover, with peaks of 90% for leukemia and lymphomas, which are also among the most common pathologies in this age group), neoplasms remain the leading cause of death from illness in childhood. Much progress has been made in recent decades on the front of therapies and early diagnosis, but Little is known about how pediatric cancers arise: for about 90 percent of cases the cause is still unknown today and it is assumed that they are due to the effect of the interaction between various external factors (most of them do not depend on environmental or lifestyle factors) with the heritage genetic of each of us, which varies greatly from person to person even within the same family. The recent discovery made by Italian researchers also goes in this direction described in a study published in the scientific journal Blood Cancer Journal
which adds a new piece to the knowledge of two different haematological neoplasms, acute lymphoblastic leukemia and myelodysplastic syndrome.
The role of hereditary genetics
We have shown for the first time that variants of a gene of the cohine family, the STAG1 gene, determine certain conditions that can increase the risk of developing leukemia and dysplasia. Giovanni Cazzaniga, Head of the Leukemia Genetics Research Unit of the Tettamanti Foundation and Associate Professor of Medical Genetics at the University of Milan Bicocca -. a new data: until a few years ago, leukemias were considered diseases without a family predisposition, but today it is known that this is not the case: we are understanding that in 5-10% of cases of pediatric blood-oncological cancers there may be hereditary genetic conditions that increase the risk. The cohine genes they were not considered among those capable, if altered, of increasing the risk of developing these pathologies. There is no immediate consequence, but certainly knowing the history of the disease in a deeper and deeper way allows us to study how to prevent its occurrence. In particular, they have been identified two variants of the STAG1 gene: the first (Arg1167Gln) was identified in a 2-year-old boy with acute lymphoblastic leukemia and the second in a 14-year-old adolescent (Arg1187Gln) with a form of myelodysplastic syndrome.
I study
The new discovery is the result of the collaboration between the researchers of the Tettamanti Foundation and colleagues from the Mario Negri Institute for Pharmacological Research, the University of Munich and the University of Dresden, made thanks to the support of the Italian Association for Cancer Research (Airc ) and the Maria Letizia Verga Committee. Scientists have performed a screening of 120 children with acute lymphoblastic leukemia, 19 children with known cases of acute lymphoblastic leukemia or acute myeloid leukemia in the family and two children with myelodysplastic syndrome. Analyzing its DNA with a technique called Ngs (next generation sequencing), they identified two germline variants of the STAG1 gene that have never been characterized before. To evaluate their possible role in tumor development predisposition, the researchers then used a model in vitro
, by growing particular cell lines (lymphoblastoids) in culture, prepared from lymphocytes taken from the peripheral blood of patients and each containing only one of the two variants identified. Comparing these cells with control cell lines obtained from healthy donors, it was seen that in the former the damage to the DNA was much greater.
Future developments
The next step of the researchers will be to try to understand through which steps and mechanisms these functional damages could lead to the onset of tumors, with the long-term goal of prevent its clinical onset. Further studies are needed to verify whether this discovery may have therapeutic implications. However, if these results are confirmed in larger case series, patients carrying these variants of the STAG1 gene may be worthy of genetic counseling to search for the presence of such mutations in other family members and possibly set up a surveillance program (currently not available for these conditions), as well as to make appropriate therapeutic decisions: avoid, for example, radiotherapywhich in itself increases the damage to DNA.
July 26, 2022 (change July 26, 2022 | 4:00 pm)
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