2026-04-17T19:16:57Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2167152025-11-19T19:20:44Zcom_2072_1057col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Sanchez Guixe, Monica author Muiños Ballester, Ferran author Pinheiro Santin, Morena author Gonzalez Huici, Victor author Rodriguez Hernandez, Carlos J. author Avgustinova, Alexandra author Lavarino, Cinzia author Gonzalez Perez, Abel David author Mora Graupera, Jaume author López Bigas, Núria author 2024-11-25T11:01:15Z 2024-11-25T11:01:15Z 2024-03-19 2024-11-20T15:05:46Z Pediatric cancers are rare diseases, and children without known germline predisposing conditions who develop a second malignancy during developmental ages are extremely rare. We present four such clinical cases and, through whole-genome and error-correcting ultra-deep duplex sequencing of tumor and normal samples, we explored the origin of the second malignancy in four children, uncovering different routes of development. The exposure to cytotoxic therapies was linked to the emergence of a secondary acute myeloid leukemia. A common somatic mutation acquired early during embryonic development was the driver of two solid malignancies in another child. In two cases, the two tumors developed from completely independent clones diverging during embryogenesis. Importantly, we demonstrate that platinum-based therapies contributed at least one order of magnitude more mutations per day of exposure than aging to normal tissues in these children. Càncer en els infants Quimioteràpia del càncer Cancer in children Cancer chemotherapy Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues