Researchers from the Cima and the Clínica Universidad de Navarra have participated in an international research that has identified new genes in the development of osteosarcoma, the most common malignant bone tumor in children and adolescents. The study, carried out in 1,244 patients, reveals that 28% of the cases analyzed present alterations in genes of hereditary predisposition, some of them not linked to development of osteosarcoma until now.

The Clinic and the Cima University of Navarra are the only Spanish institutions involved in this research, promoted by the high school National Cancer Institute (NCI) and the high school National Institutes of Health in Bethesda, Maryland, (USA). A total of twenty American and European healthcare institutions have participated in the finding project. The results were recently published in JAMA Oncologyone of the most important international scientific journals in its field specialization program.

The work has identified germline (inherited), highly penetrant mutations in more than a quarter of osteosarcoma patients who had not been selected for family history. "An issue that required additional follow-up analysis and possible genetic counseling with cascade family testing," stresses Dr. Ana Patiño García, director of the Genomic Medicine Unit at Clínica Universidad de Navarra and a participant in the international study, together with Dr. Miriam Gutiérrez, a specialist at the Clinic's Pediatrics department , and Dr. Fernando Lecanda, researcher and director of laboratory of Adhesion and Metastasis at Cima University of Navarra.

Massive sequencing

For the research, ten of the participating institutions (including the Clinic and the Cima) sequenced the whole exome (coding part of all genes) in 1,244 patients with osteosarcoma. The results were compared with DNA from 1,062 individuals without cancer. In the analysis, 238 genes of high interest were evaluated for their association with cancer susceptibility, followed by testing of mutational load in 736 additional candidate genes. 

Historically we have known that the development of osteosarcoma was linked to three very specific hereditary syndromes: Li-Fraumeni, Werner and Rothmund-Thomson," says Dr. Patiño. We geneticists thought that, apart from these genes, 99% of osteosarcomas presented with no apparent hereditary cause and that, in general, they were due to sporadic mutations produced by other unknown factors".

More ambitious genetic analyses

The results of this study conclude the need to "evaluate all subject of hereditary predisposition syndromes in those family nuclei in which there is a certain coincidence of osteosarcoma with other tumors". goal Once these mutations have been identified, the specialist suggests the need to propose a genetic committee to the affected families, with the aim of reducing, or at least monitoring, the risk of developing the disease.

Dr. Fernando Lecanda, of the Cima University of Navarra, points out that "progress has been made B in the "genomic mapping" of this tumor. We now have the possibility of doing these massive genetic programs of study quickly and affordably, so we should not limit ourselves to the "usual suspect" genes. We should be a bit more ambitious in genetic analyses, extending them to all genes whose clinical relevance is known."

issue The authors consider that this subject of scientific publications, "are the result of the coalescence of a great international effort, in which many centers have been involved without which it would be impossible to gather such a high number of cases in this rare tumor. All this under the leadership of the NCI in the USA. One more example that, as in other fields, science has no borders either".