Scientists at Cleveland Clinic Children have uncovered a previously unrecognized gene that heightens the likelihood of developing osteosarcoma, the most common malignant bone tumor in youngsters and young adults.
In a paper in the Journal of Clinical Oncology, the group examined genomic data from nearly 6,000 paediatric cancer patients and compared it with over 14,000 cancer‑free adults. Using public databases and computational prediction tools, the investigators focused on 189 genes involved in various DNA‑repair pathways.
The analysis showed that inherited alterations in certain DNA‑repair genes can increase cancer risk. One gene, SMARCAL1, emerged as a notable risk factor for osteosarcoma. About 2.6 % of children with this disease carry inherited SMARCAL1 mutations, which may weaken DNA repair mechanisms and foster tumour growth.
"These findings deepen our understanding of osteosarcoma biology, enabling earlier detection and opening possibilities for targeted therapies," said senior author Dr. Richa Sharma, MD, a paediatric haematologist‑oncologist at Cleveland Clinic Children. "With limited progress in treating osteosarcoma over the last four decades, this discovery could lead to significant advances for patients."
Osteosarcoma most often arises in long bones of the arms or legs, manifesting as bone pain, a lump or swelling, and fractures that occur easily. Experts estimate fewer than 1,000 cases occur in the U.S. each year. When the disease stays localized, roughly 70 % of patients survive, whereas survival drops to about 20 % if it has spread beyond the original bone.
The study was conducted in partnership with researchers from St. Jude’s Children’s Research Hospital, Mayo Clinic, and Kitz Höpp Children’s Cancer Centre Heidelberg in Germany.