Blood Antibody Signals May Offer Clues to the Origins of Childhood Cancer

Pediatric cancers, including leukemia, myeloma, neuroblastoma and osteosarcoma, differ from adult cancers in their causes, location, tumor type and treatment response. Children have had less time to accumulate DNA damage from environmental stressors, lifestyle factors and aging, and their tumors tend to carry fewer mutations and arise from less mature cells. New findings offer further insight into these cancers’ origins, suggesting that abnormal antibodies targeting DNA repair proteins may contribute to their development.

University of Bergen (Bergen, Norway) scientists and colleagues identified elevated levels of IgG autoantibodies against DNA repair proteins in children with cancer. The antibodies primarily targeted proteins encoded by RAD52, NUMA1, ALKBH7, APBB1, UNG and MGMT, genes closely involved in DNA repair that were not significantly mutated in these cancers. Follow-up experiments showed that the autoantibodies can enter cells, particularly as cells complete their growth phase and prepare to divide. Once inside, they appear to concentrate in the TIGER organelle, where transcription factors and other short-lived essential proteins are produced and modified.

Image: The discovery could enable early screening of young children, with the long-term goal of preventing pediatric cancers from developing later in childhood. (Image Credit: Shutterstock)

To investigate these antibody patterns, the team characterized the proteome in tumor and blood samples from 175 adults and children with sarcoma or acute lymphoblastic leukemia. Samples were collected between 2014 and 2017 through the NoSarC Norwegian Sarcoma Study, the Norwegian Childhood Cancer Biobank and the Oslo University Hospital Cancer Research Biobank. They were compared with samples from anonymized healthy individuals, including blood donors and children in Bergen.

To explore whether the antibodies could precede a cancer diagnosis, the scientists also examined selected samples from 59 school-age children in the Avon Longitudinal Study of Parents and Children and Born in Bradford cohort studies, approximately half of whom later developed cancer before age 30.

Children aged two to 19 years with pediatric cancer had substantially higher levels of circulating IgG antibodies against DNA repair proteins than young adults and older individuals. In the selected childhood cohort, those who later developed cancer were about eight times more likely than healthy peers to have antibodies against at least one core antigen involved in DNA repair. Cancer developed an average of six years after blood sampling, suggesting that these antibody signals may be detectable well before diagnosis. 

Published in Frontiers in Immunology on October 14, 2026, the findings raise the possibility of screening for an autoimmune predisposition to cancer, while further cell-based studies continue to investigate the underlying mechanism.

“We showed that many children with various types of cancer have antibodies against some of their own DNA repair proteins. We also demonstrated that such ‘auto-antibodies’ can enter live cells and bind to – and probably inhibit – the activity of these essential proteins,” said Dr Ola Myklebost, an emeritus professor of molecular oncology at the University of Bergen.

“At present we are investigating the effect of patient antibodies on the repair of induced mutations in cultured cells. Ultimately, we hope to clone white blood cells that secrete such auto-antibodies, and test for any cancer-causing effects in mice to definitively prove our hypothesis,” added Dr Myklebost.

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