Causes of cancer also found in 'junk DNA'

Scientists have called it 'junk DNA', Junk DNA. It is that portion of the genome that, according to current knowledge, has no functional role in the biological activities of the cell. Sequences also called noncoding DNA, which make up about 99 percent of the human genome and are little explored ground today because of its alleged uselessness.

Researchers at CEINGE-Advanced Biotechnology in Naples wanted to 'consider' it and, through the use of state-of-the-art sequencing technologies, found that 'junk DNA' is far from 'useless' and that, on the contrary, cancer-causing elements can be traced in it.

In particular, the research group of Mario Capasso and Achille Iolascon, Principal Investigator of CEINGE and respectively, associate and full professor of Medical Genetics at the University of Naples Federico II, examined 151 cases of neuroblastoma, one of the most aggressive and widespread peripheral nervous system tumors that affects children in the first years of life. They analyzed them using state-of-the-art sequencing methods(Next Generation Sequencing) and found that mutations are present in Junk DNA that may participate in tumor development.

The research, which was of considerable magnitude, both in terms of the amount of cases analyzed (151 neuroblastoma patients) and the complexity of the investigation itself (advanced sequencing of the entire genome of the 151 patients was carried out), was published in one of the most authoritative international scientific journals, Cancer Research of the American Association for Cancer Research.

The surprising result was also thanks to the work of Vito Alessandro Lasorsa, Ph.D. student at the University of Naples Federico II, who developed a bioinformatics analysis method in which noncoding DNA mutations were classified according to their genomic context. The researchers used data from advanced whole-genome sequencing of 151 neuroblastoma patients and public data from the ENCODE project to 'contextualize' mutations found in 'junk' DNA.

"In recent years, the development and dissemination of massive DNA sequencing methods, termed 'Next Generation Sequencing,'" explains Achille Iolascon, "has led to tremendous advances in both diagnostics and research. Indeed, these techniques have changed the way researchers and clinicians think. The search for DNA mutations has, therefore, become more immediate, but still not simple. Today it is known that the Junk portion of the human genome carries regions essential for remote regulation of gene function. It seems clear that mutations in these regions of the genome may also play a role in cancer development."

Previous studies by Professor Capasso and Professor Iolascon and other European and American groups had already led to the identification of mutations that directly affect genes associated with neuroblastoma development. Those findings had also highlighted that the number of tumors affected by these gene mutations is low (about 8 percent). So far, therefore, only a fraction of the questions from researchers, but especially from young patients, have been answered.

"This work adds an important piece to the knowledge of 'junk' DNA, which," concludes Mario Capasso, "in light of these new results, seems far from being a useless and throw-away element, but a new ground to explore. Another relevant aspect of this study is that the innovative DNA analysis method used can be applied to other types of cancer and can thus increase knowledge of the underlying causes of this devastating disease. In addition, new research may, based on these results, develop new, more targeted and less invasive therapies for those patients affected by the most aggressive stages that are resistant to classical therapies."

The kind of research carried out by CEINGE researchers has very high costs and was made possible by funding from charities. With the support of the Italian Association for Research Against Cancer(AIRC), the Association of Pediatric Oncology and Neuroblastoma(OPEN) and the Italian Foundation for the Fight against Neuroblastoma, the group of professors Capasso and Iolascon is able to carry on their work and give hope for life to children with cancer.