Study Finds 69 Mutation Signatures in 611 Childhood Tumors, With Chemotherapy Driving Relapse Scars
Updated
Updated · Nature.com · Jul 22
Study Finds 69 Mutation Signatures in 611 Childhood Tumors, With Chemotherapy Driving Relapse Scars
1 articles · Updated · Nature.com · Jul 22
Summary
Whole-genome analysis of 611 tumors from 544 children found chemotherapy and radiotherapy were the only detectable external mutagens in relapsed childhood cancers, often becoming the dominant source of DNA damage.
Post-therapy tumors carried nearly 3 times more private mutational signatures and about 2 times the total somatic mutation burden than treatment-naive cancers, with platinum drugs causing the highest variant counts in most exposed patients.
Researchers identified 69 SBS, DBS and indel signatures—20 novel and 15 seen only in treated tumors—and estimated that four chemotherapies alone accounted for 15.1% of point mutations across the cohort.
Platinum-associated mutations could appear as early as 91 days after treatment began, and 35% of platinum-treated tumors showed detectable platinum signatures within 12 months, rising to 48% by 18 months.
Signature-positive tumors also showed resistance-linked gene overexpression and worse outcomes in pediatric and adult validation cohorts, suggesting treatment scars could help track emerging resistant clones and support therapy de-escalation.
If chemotherapy fuels cancer's evolution, how can we design safer treatments for children?
Can real-time genomic tracking predict and prevent treatment-induced tumor relapse before it happens?
Therapy-Induced Mutational Signatures in Childhood Cancer: Breakthroughs in Relapse, Resistance, and Long-Term Care
Overview
A groundbreaking study published in Nature reveals that chemotherapy and other cancer treatments can leave distinct genetic 'scars' in childhood cancers that return after treatment. These therapy-induced mutations shape the genetic landscape of relapsed tumors, offering new insights into how cancer evolves and adapts after therapy. Understanding these specific mutation profiles is a major step forward, as it helps explain why some cancers become resistant and recur. This research marks a critical advancement in pediatric oncology, highlighting the complex relationship between cancer treatments and the long-term genetic changes they cause in young patients.