(MEMPHIS, Tenn. \u2013 April 19, 2026) Scientists at St. Jude Children\u2019s Research Hospital today report how lifesaving childhood cancer treatments leave \u201cfingerprints\u201d on DNA, which can lead to second neoplasms (cancers or cancer-like diseases) decades later. The discovery may provide a path toward reducing long-term risks of pediatric cancer therapy by improving surveillance and early detection of secondary disease for survivors. The findings were published today in Cancer Discovery, a journal of the American Association for Cancer Research.<\/p>\n
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Childhood cancer survival has improved dramatically, but many survivors face long-term health risks well into adulthood. Until now, the direct biological link between specific pediatric cancer therapies and subsequent neoplasms has been difficult to define. To address this gap, St. Jude researchers analyzed genetic mutations in the subsequent neoplasm tumor tissue of 160 survivors who developed subsequent breast, thyroid malignancies and mengiomas, searching for patterns tied specifically to earlier treatments.<\/p>\n
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\u201cWe found that lifesaving radiation and chemotherapy treatments that cure childhood cancer also leave specific mutational signatures or \u2018fingerprints\u2019 in the DNA of second neoplasms,\u201d said first and corresponding author Samuel Brady<\/a>, PhD, St. Jude Department of Pharmacy & Pharmaceutical Sciences<\/a>. \u201cThese findings give us an opportunity to rethink how therapies are delivered to reduce risk, while also improving screening protocols to detect secondary cancers earlier.\u201d<\/p>\n \u00a0<\/p>\n Finding childhood cancer treatment\u2019s DNA fingerprints<\/p>\n \u00a0<\/p>\n While previous research had linked certain therapies, such as radiation, to survivors\u2019 increased cancer risk, this new study establishes a direct molecular connection. To find these direct connections and rule out normal aging-related mutations, the researchers looked at whole-genome, whole-exome and RNA-sequencing of second neoplasm samples from survivors enrolled in the Childhood Cancer Survivor Study<\/a> (CCSS). They then compared those sequences to similar cancers in the general population, revealing recurring mutational patterns in survivors who received specific treatments.<\/p>\n \u00a0<\/p>\n \u201cWe are the first to show direct causality between childhood cancer treatments and second neoplasms,\u201d said co-senior author Jinghui Zhang<\/a>, PhD, St. Jude Department of Computational Biology<\/a>. \u201cWe found that the DNA-mutating effects of treatments are imprinted into the genomes of secondary cancers that emerged 20 to 30 years later, giving us new insights into how we could reduce treatment toxicity.\u201d<\/p>\n \u00a0<\/p>\n Radiation therapy was associated with the most frequent and largest DNA alterations, as well as the highest risk of secondary thyroid cancer. Chemotherapy agents also left identifiable signatures. Nitrogen mustards and platinum-containing agents caused smaller changes in DNA. However, the location of these mutations differed by drug type, which could lead to different outcomes. For example, platinum agents sometimes preferentially mutated the gene NF2, leading to a greater risk of a brain tumor called meningioma. These therapy-specific patterns could help clinicians anticipate which secondary cancers are most likely to develop.<\/p>\n \u00a0<\/p>\n \u201cIn the last few decades, we have been very effective in developing treatments that save children\u2019s lives,\u201d said David Ellison<\/a>, MD, PhD, FRCP, FRCPath, FRCPCH, St. Jude Department of Pathology<\/a> chair. \u201cBy defining how these therapies mutate DNA in predictable ways, we can better understand and address the long-term consequences of these treatments.\u201d<\/p>\n \u00a0<\/p>\n Toward safer therapies and better survivor care<\/p>\n \u00a0<\/p>\n Together, these findings provide a framework for improving long-term outcomes for survivors of childhood cancer. By understanding how specific therapies alter DNA, researchers may be able to modify treatments to reduce harmful mutations, develop targeted therapies that avoid high-risk pathways and tailor surveillance strategies based on an individual\u2019s treatment history to detect second neoplasms at their earliest, most treatable stage.<\/p>\n \u00a0<\/p>\n \u201cThese results represent an important step toward more personalized survivorship care,\u201d said co-senior author Greg Armstrong<\/a>, MD, MSCE, St. Jude Department of Epidemiology & Cancer Control<\/a> chair. \u201cBy linking specific treatments to future risk, we can better protect survivors not just during therapy, but throughout their lives.\u201d<\/p>\n \u00a0<\/p>\n Authors and funding<\/p>\n The study\u2019s other authors are Michael Arnold, University of Colorado; Kayla Stratton and Wendy Leisenring, Fred Hutchinson Cancer Center; Maria Gramatges, Baylor College of Medicine; Lucie Turcotte, Cindy Im and Joseph Neglia, University of Minnesota; Rebecca Howell, University of Texas MD Anderson Cancer Center; Miriam Conces, Nationwide Children\u2019s Hospital; Smita Bhatia, University of Alabama at Birmingham; and Mingjuan Wang, Ramzi Alsallaq, Li Dong, Mohammad Khan, Wentao Yang, Wei Liu, Yan Chen, Emily Plyler, Jacob Steele, Brent Powers, David Rosenfeld, Michael Edmonson, Yuan Feng, Nadezhda Terekhanova, Kohei Hagiwara, Sasi Arunachalam, Heather Mulder, Deo Srivastava, Michael Rusch, Vikki Nolan, Aaron McDonald, Yadav Sapkota, John Easton, Xiaotu Ma, Zhaoming Wang and Yutaka Yasui, St. Jude.<\/p>\n \u00a0<\/p>\n The study was supported by grants from the National Cancer Institute (U24 grant 3U24CA055727, 3U24CA055727-28S1, P30 CA021765) and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising and awareness organization of St. Jude.<\/p>\n St. Jude Media Relations Contact<\/p>\n Michael Sheffield Desk: (901) 595-0221 Cell: (901) 379-6072 michael.sheffield@stjude.org<\/a> media@stjude.org<\/a><\/p>\n \u00a0<\/p>\n St. Jude\u00a0Children’s Research Hospital<\/p>\n St. Jude\u00a0Children\u2019s Research Hospital is leading the way the world understands, treats, and cures childhood catastrophic diseases. As the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children,\u00a0St. Jude\u00a0advances groundbreaking research and shares its discoveries worldwide to accelerate progress in pediatric medicine. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to more than 80% since the hospital opened more than 60 years ago. Through collaboration and innovation,\u00a0St. Jude\u00a0is working to ensure that children everywhere have access to the best possible care.\u00a0To learn more, visit\u00a0stjude.org<\/a>,\u00a0read\u00a0St. Jude\u00a0Progress,\u00a0a digital magazine<\/a>,\u00a0and follow\u00a0St. Jude\u00a0on social media at\u00a0@stjuderesearch<\/a>.<\/p>\n \t\t\t\t\t\t\t\t\t\t