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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/216715
Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues
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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.
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SANCHEZ GUIXE, Monica, MUIÑOS BALLESTER, Ferran, PINHEIRO SANTIN, Morena, GONZALEZ HUICI, Victor, RODRIGUEZ HERNANDEZ, Carlos j., AVGUSTINOVA, Alexandra, LAVARINO, Cinzia, GONZALEZ PEREZ, Abel david, MORA GRAUPERA, Jaume, LÓPEZ BIGAS, Núria. Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues. _Cancer Discovery_. 2024. Vol. 14, núm. 6, pàgs. 953-964. [consulta: 23 de gener de 2026]. ISSN: 2159-8290. [Disponible a: https://hdl.handle.net/2445/216715]