Study links changes in the SMARCAL1 gene to increased risk for bone cancer

Children can be at a higher risk of developing cancer, based on variants present in their body’s cells. While genes involved in the recognition and repair of DNA damage are known to be often mutated in tumor cells, it has been unclear how variants in these same genes, when present in normal or germline cells, predispose children to certain cancers.

A study co-led by Kim Nichols, MD, Director of the St. Jude Cancer Predisposition Division and member of the Department of Oncology, and Richa Sharma, MD, formerly of St. Jude, now of Cleveland Clinic Children’s, performed the first comprehensive analysis of DNA repair gene variants and childhood cancer predisposition, looking at germline DNA sequence information from almost 6,000 children with cancer. They found that variations in SMARCAL1, a gene that encodes an important DNA repair protein, are associated with increased risk for a type of bone cancer called osteosarcoma. The analysis also confirmed several known predisposing variants in other cancer-associated genes, increasing confidence in the findings. The results were published in the Journal of Clinical Oncology. 

“We are very excited about these findings because they provide new insights into the development of osteosarcoma, an aggressive cancer for which there has been little improvement in therapy for several decades. In addition, genetic testing for germline SMARCAL1 gene changes will help to identify individuals who might benefit from screening to detect new osteosarcoma tumors at their earliest and most curable stages,” Nichols said.

“Defects in DNA repair pathways are key enablers of cancer. We established SMARCAL1, a DNA repair gene, to predispose children to osteosarcoma, which not only impacts the clinical care for patients with osteosarcoma but may help us better understand how this aggressive bone cancer develops,” Sharma said.

“By harnessing one of the largest pediatric cancer datasets and applying an unbiased analytic framework, we underscore the importance of DNA damage response pathways in pediatric cancer risk. This data-driven approach not only sheds light on SMARCAL1’s role in osteosarcoma but also provides a scalable framework to explore additional gene sets of interest,” said first author Ninad Oak, PhD, Department of Oncology.

Read more